In vitro and in vivo antibacterial activity of AB-206 was examined using various strains of both gram-positive and gram-negative bacteria. The results are summarized as follows:
1. AB-206 showed a potent antibacterial activity against gram-negative bacteria and was found to be more active than piromidic acid and nalidixic acid.
2. It was characteristic that AB-206 also showed the antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus and nalidixic acid-resistant strains of bacteria.
3. AB-206 was generally bactericidal against various species of gram-negative bacteria including E. coli, Proteus, Klebsiella pneumoniae and Pseudomonas aeruginosa
4. Oral administration of AB-206 showed greater antibacterial activity than nalidixic acid in the experimental infection of mice with E. coli, Klebsiella pneumoniae and Proteus morganii.

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The present study was carried out in order to determine the in vitro and in vivo antibacterial activities of AB-206 and following results were obtained.
1. AB-206 was found to exhibit potent antibacterial activity chiefly against gram-negative bacilli, and in particular its activity against enterococci and non-glucose fermenting gram-negative bacilli including P. aeruginosa was stronger than that of PPA or NA.
2. In experimentally induced infections of Serratia, P. aeruginosa and P. cepacia in mice, AB-206 was proven to be effective by oral route. Its ED₅₀ was lower than that of PPA, DOTC or GM.

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The antibacterial activity of AB-206 was determined for a total of 790 strains of Staphylococcus aureus, Haemophilus infiuenzae, Enterobacter, Proteus (Pr. vulgaris, Pr. mirabilis, Pr. morganii, Pr. rettgeri and Pr. inconstans), Serratia marcescens, Pseudomonas (Ps. maltophilia, Ps. putida, Ps. fiuorescens and Ps. cepacia), Achromobacter xylosoxidans, Flavobacterium (F. meningosepticum, F. sp.), Acinetobacter calcoaceticus and Alcaligenes faecalis isolated from various clinical materials at Clinical Laboratories of Juntendo University Hospital during the period from late 1976 to early 1977, and comparisons were made with that of NA, PA, PPA and other antibiotics in ordinary use.
1) AB-206 was equally active as ABPC against H. influenzae.
2) When compared with GM, AB-206 was more active against flve species of Proteus and Serratia marcescens and almost equally active against Enterobacter.
3) The antibacterial activity of AB-206 against four species of Pseudomonas varied according to the species of the organisms, with rather strong activity against Ps. cepacia and relatively weak activity against the other three species of organisms.
4) Against Acinetobacter calcoaceticus, the antibacterial activity shown by AB-206 was inferior to that of MINO and DOTC and equal to that of GM.
5) Although the antibacterial activity of AB-206 against Achromobacter xylosoxidans was weak, more than half strains of Flavobacterium and Alcaligenes had low MIC of AB-206.
6) When compared with NA, PA and PPA, AB-206 showed higher antibacterial activity against any of the strains tested in this study.

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The in vitro and in vivo antibacterial activity of AB-206 was compared with those of nalidixic acid (NA) and pipemidic acid (PPA). The following results were obtained.
1) The antibacterial activity of AB-206 against Gram-negative bacteria was superior to those of NA and PPA.
2) The in vitro antibacterial activity of AB-206 against clinical isolates of Staphylococcus aureus, Escherichia coli, Proteus species, Klebsiella pneumoniae and Serratia marcescens was superior to those of NA and PPA, but was inferior to PPA for Pseudomonas aeruginosa.
3) Influence of medium pH, the addition of horse serum and inoculum size on in vitro antibacterial activity of AB-206 showed the same tendency to NA and PPA.
4) Bactericidal action of AB-206 against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa was similar to those of NA and PPA.
5) Frequency of natural resistant mutants to AB-206 was lower than NA and PA.
6) On the protecting effect for systemic infections in mice, the effect of AB-206 was superior to NA and PPA for Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa.

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The most effective administration of a new chemotherapeutic agents, AB-206, has been studied in the experimental mice infection with Pseudomonas aeruginosa.
1) Pseudomonas aeruginosa damaged by AB-206 or pipemidic acid (PPA), when the drug was free, began regrowth after a lag time in vitro.
2) The therapeutic efficacy of AB-206 or PPA on multiple administration was as effective as its single administration.
3) An important factor to decide the therapeutic efficacy of AB-206 and PPA was the high drug concentration in plasma and peritoneal fluid.

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AB-206, 5, 8-dihydro-5-methoxy-8-oxo-2 H-1, 3-dioxolo [4, 5-g] quinoline-7-carboxylic acid, is a novel chemotherapeutic agent. Its in vitro and in vivo antibacterial activities were investigated and the results were as follows;
AB-206 had very potent antibacterial activities on Enterobacteriaceae, Haemophilus and Neisseriain gram-negatives and the inhibitory activities of AB-206 on these bacteria were 8-16 times more potent than those of nalidixic acid and 32-64 times than those of piromidic acid. Moreover, since AB-206 was active on Pseudomonas aeruginosa and Acinetobacter in glucose-non-fermenting bacteria, Staphylococci and some of anaerobes, AB-206 had the more potent antibacterial activities and wider spectrum than the reference drugs such as nalidixic acid and piromidic acid.
The antibacterial activities of AB-206 were little influenced by changing medium, pH (6-8) and inoculum size. Binding rate of AB-206 with human serum and inactivating rates of AB-206 by addition of human serum were less than those of nalidixic acid.
In vivo antibacterial activities were investigated by using systemic infections of E. coli, K. pneumoniae, Proteus and S. marcescens in mice. The values of ED₅₀ in AB-206 on these experimental infections were 1/4-1/2 of those of nalidixic acid by oral administration in one, two or three divided doses. The values of ED₅₀ by single administration of AB-260 were almost equal to these of ED₅₀of total administration in two and three divided doses. AB-206 did not show the protecting activity on the infection of Streptococcus pyogenes which was insusceptible to AB-206 in vitro.

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This study was undertaken to compare the changes of the fecal microflora and increase of cecal weights of mice following the oral administration of AB-206, nalidixic acid and erythromycin at 50mg/kg twice daily for 10 days. The numbers of aerobic and anaerobic bacteria except Enterobacteriaceae of fecal microflora were not changed by the administration of AB-206 and the recovery of normal microflora was observed over the administration period. The appearance of resistant strain and increase of cecal weights in mice were not detected by the oral administration of AB-206.

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The bioassay method of AB-206 was investigated by using various media, assay organisms and inoculum sizes and the results were as follows:
Since AB-206 was insoluble in water at acidic and neutral pH, it was dissolved at 5 mg/ml in 1%sodium bicarbonate aqueous solution. This solution is able to be stocked in a brown bottle but it is desirable to make it just before use.
AB-206 standard calibration line was prepared in Moni-Trol I and animal serum for the determination of serum level of human and animal respectively and in M/15 phosphate buffer (pH 7.4) to determine level in urine, bile, tissue homogenates and feces. The AB-206 solution (5 mg/ml) was serially 2-fold diluted to give concentrations of 10 to 0.1μg/ml.
E. coli Kp, employed as the assay organism, was harvested in heart infusion broth from nutrient agar slants, and 0.5 ml of this suspension was used to inoculate into 100 ml of melted modified Mueller-Hinton agar (Nissui). A 10 ml amount of this seeded agar was poured to Petri-dishes (9 cm diameter). Four or six stainless-steel cylinder cups were placed on the solidified surface of each plate. The standard solutions or unknown samples were placed into the cups and the dishes were incubated for 18 hr. at 37°C, and the zones of inhibition were measured.
The biological activity in serum was determined from the standard curve which was constructed by a standard serum solution and to determine the levels in urine, bile, tissue homogenates and feces, the standard curve by using M/15 phosphate buffer was employed.

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AB-206, a novel chemotherapeutic agent active against gram-negative bacteria, was administered to mice, rats, Beagle dogs and Rhesus monkeys at a single oral dose of 10-100 mg/kg and absorption, distribution and excretion were investigated by bioassay using E. coli Kp. The results were as follows:
AB-206 was absorbed well and rapidly appeared in serum. At a dose of 50mg/kg, mean peak levels in serum were 37-67μg/ml. Dose response and species difference of serum level in these animals were observed.
About 1.4-6.5% of active AB-206 were excreted into urine for 24 hr.postadministration and their mean urine levels of AB-206 were fully beyond the MICs on many gram-negative bacteria.
High bile levels of AB-206 in rats were observed and the recovery rate reached about 5% in 24 hr. postadministration.
The highest AB-206 concentrations in tissues were observed in lung and kidney but their concentrations were below the serum levels and the levels in liver were the lowest. High antibacterial concentrations in gastrointestinal tracts in mice and rats except for caecum and rectum in mice were observed during 4hr. postadministration. But fecal recovery rates of antibacterial activity in mice, rats and monkeys were below 0.2% of dosage.

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Absorption, distribution and excretion of 5, 8-dihydro-5-methoxy-2 H-8-oxo-1, 3-dioxolo [4, 5-g] quinoline-7-carboxylic acid (AB-206), a new synthetic antimicrobial agent, were examined in mice, rats, dogs and monkeys after single oral administration of 50 mg/kg of ¹⁴C-labelled AB-206.
In rats, dogs and monkeys, the peak serum levels of ¹⁴C existed at 1 hr. after administration were 45, 41 and 69μg equivalents of AB-206 per ml, respectively, while in mice the peak level existed at 0.5 hr. was 42μg Eq/ml. The half-life of the serum levels was about 1.3 hr. in mice and monkeys, and about 2.2 hr. in rats and dogs.
In tissues examined, the maximum levels of ¹⁴C were found at 0.5 hr. in mice and at 1 hr. in rats. The levels rapidly declined and were negligible by 24 hr. In both species, liver and kidney showed relatively high concentrations of ¹⁴C while brain showed much low concentrations.
The excretion of ¹⁴C in rats and dogs showed a similar pattern. In both species the fecal ¹⁴C (60-70% of the dose during 48 hr. period) was higher than the urinary ¹⁴C (20-30%). In contrast, mice and monkeys excreted more ¹⁴C in urine (60-65%) than in feces (20-25%). In rats, the biliary excretion of ¹⁴C was 40% of the dose within 24 hr. period, but the enterohepatic circulation of ¹⁴C was scarcely observed.

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The metabolism of 5, 8-dihydro-5-methoxy-8-oxo-2H-1, 3-dioxolo [4, 5-g] quinoline-7-carboxy licacid AB-206, a new antimicrobial agent, in mice, rats, dogs and monkeys was studied by using ¹⁴C-AB-206, which was administered orally to the animals in a dosage of 50 mg/kg. The radioactive metabolites in serum, urine, feces, bile (rat), liver (rat) and kidney (rat) were analysed by TLC and HLC. The results are summarized as follows.
1. AB-206 was biotransformed by the animals to at least seven identified metabolites ; 5, 8-dihydro-8-oxo-2 H-1, 3-dioxolo [4, 5-g] quinoline-7-carboxylic acid (M-1), 1, 4-dihydro-7-hydroxy-1; 6-dimethoxy-4-oxoquinoline-3-carboxylic acid (M-2), 1, 4-dihydro-6, 7-dihydroxy-4-oxoquinoline-3-carboxylic acid (M-3), and the glucuronides of AB-206, M-1, M-2 and M-3.
2. In the serum, the peak concentrations of intact AB-206 in rats, dogs, mice and monkeys were 28, 35, 37 and 45μg/ml respectively ; the major metabolite was the glucuronide of AB-206 (5-18μg/ml at the peak) and M-1 was found only in monkeys as a minor metabolite.
3. The recovery rates of intact AB-206 were 2-7% of the dose in the urine (0-24 hr.), 5% in the bile of rats (0-20 hr.) and 2% in the feces of monkeys (0-24 hr.). The major metabolite in the urine (0-24 hr.) was the glucuronide of AB-206 as shown in the recovery rates of 17% in rats, 7% in dogs, 32% in mice and 33% in monkeys. M-1 (3-7%), M-2, M-3 and the glucuronide of M-1 were found in the urine as minor metabolites. In the feces, M-1 and M-2 (not detected in monkeys) were found as the major metabolites and their glucuoronides as the minors. The main metabolites in the bile of rats consisted of the glucuronides of M-2 (12% of the dose) and M-3 (7%).
4. The peak concentrations of intact AB-206 in the liver and the kidney of rats were 16 and 29μg/g respectively, and M-1, M-2 and the glucuronides of AB-206, M-1 and M-2 were found as metabolites.
Absorption, distribution and excretion of ¹⁴C-labelled M-1 in rats were examined after oral administration at 50 mg/kg of the dose. It was found that M-1 was scarcely absorbed orally and excreted into the feces. The blood level of ¹⁴C was 0.64μg/ml at the peak. The urinary ¹⁴C recovered during 48 hr. was only 2.7% of the dose while the fecal ¹⁴C was 80%.

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Absorption, distribution, excretion and metabolism of 5, 8-dihydro-5-methoxy-8-oxo-2 H-1, 3-dioxolo [4, 5-g] quinoline-7-carboxylic acid (AB-206), a new antimicrobial agent, were examined in rats after multiple oral administration of 50 and 200 mg/kg/day of ¹⁴C-labelled AB-206 for 21 days, and the effect of age on the metabolism of AB-206 was also examined in different-aged rats. The results are summarized as follows.
1. The blood levels of ¹⁴C during 2 to 6 hr periods after daily doses for 21 consecutive days were higher than those of single administration but thereafter decreased as low as the latter; the peak levels being 26μgEq/ml (50 mg/kg) and 43μlgEq/ml (200 mg/kg).
2. With both dosages, the concentrations of ¹⁴C in the tissues examined at 24 hr. after 21 consecutive doses showed the values not higher than those of single administration. By 144 hr. postadministration only traces of ¹⁴C (below 1μgEq/g) remained in all of the examined tissues except gastrointestinal tracts.
3. During the consecutive dosing with both dosages of 50 and 200 mg/kg, the rats excreted ¹⁴C into urine and feces in almost constant recovery rates: 30% of the dose in urine and 60% in eces. The total recovery rate of ¹⁴C in urine and feces reached 120% of the last dose by 144 hr. postadministration.
4. The urine samples were analysed by TLC and HLC, and intact AB-206, 5, 8-dihydro-8-oxo-2 H-1, 3-dioxolo [4, 5-g] quinoline-7-carboxylic acid (M-1) and the glucuronide of AB-206 were detected. It was observed with both dosages that the ratio of intact AB-206 in the urinary ¹⁴C increased according to multiple dosings while those of M-1 and the glucuronide of AB-206 decreased. When ¹⁴C-AB-206 was administered to the different-aged rats, the similar tendency was observed with increasing of age (6 to 9 weeks-old).

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The metabolism of 5, 8-dihydro-5-methoxy-8-oxo-2 H-1, 3-dioxolo [4, 5-g]-quinoline-7-carboxylic acid (AB-206), a new antimicrobial agent, was studied in man. Intact AB-206 and its metabolites in serum, urine, feces and bile were assayed by HLC.
The serum and urine samples were collected from six healthy adults dosed orally with 500mg of AB-206. In the serum, the peak levels of intact AB-206 were observed within 3 hr. after administration and the average concentration was 6.0μg/ml. The glucuronide of AB-206 was detected as a metabolite in the serum but the concentrations were as low as 1/2 to 1/10 of those of intact AB-206. In the urine, the average concentration of intact AB-206 was 39μg/ml at the peak which was observed during 2-4 hr. periods after administration and the total recovery rate within 8 hr. was 2.2% of the dose. The major metabolite found in the urine was the glucuronide of AB-206 (24% of the dose within 8 hr.). Other metabolites detected in the urine were 5, 8-dihydro-8-oxo-2 H-1, 3-dioxolo [4, 5-g] quinoline-7-carboxylic acid (M-1)(0.02% of the dose) and the glucuronide of 1, 4-dihydro-7-hydroxy-1, 6-dimethoxy-4-oxoquinoline-3-carboxylic acid (M-2)(2% of the dose).
In the bile which was collected from the patients administered orally with 1g of AB-206, the concentration of intact AB-206 reached 82μg/ml at the highest. The biliary metabolites were the glucuronides of AB-206, M-1 and M-2, and unconjugated M-1 was also detected in one case.
In the feces which was obtained from the patient treated with 2g/day of AB-206, intact AB-206 was detected in the concentrations of 40-50μg/g. The metabolites found in the feces were M-1 and M-2.

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We carried out fundamental and clinical studies on the new antimicrobial agent, AB-206, and obtained the following results:
1) Antimicrobial activity
AB-206 exhibited quite excellent antimicrobial activity against E. coli, Proteus spp. and K. pneumoniae, good against Ps. aeruginosa.
Comparing with nalidixic acid and piromidic acid in antimicrobial activity, AB-206 was far more excellent in these organisms.
2) Serum concentration and urinary excretion
The highest serum concentrations were 3.6μg/ml at 2 hours after single 500 mg oral administration and 1.5μg/ml at 2 hours after 250 mg oral administration to 3 healthy volunteers. Urinary recoverys at those time were 5.5% in average in the former, and 4.1% in average in the latter.
3) Clinical studies
Twenty-five cases with acute simple urinary tract infection and 15 cases with chronic complicated urinary tract infection were treated with AB-206, ranging from 0.75 to 2.0g in daily dose.
In the former group, excellent clinical response was revealed in 20 and good in 5 cases. In the latter, excellent in 2, good in 8, and poor in 5 cases.
As for side effect, epigastric discomfort was complained in 3 cases, but laboratory examinations revealed no significant changes.

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AB-206 (5, 8-dihydro-5-methoxy-8-oxo-2 H-1, 3-dioxolo-[4, 5-g] quinoline-7-carboxylic acid) was administered orally to a total of 22 cases of various urinary tract infections in dosages of 500 to 1, 500 mg/day for a period of 3 to 10 days. The following results were obtained.
1) Among 6 cases of acute simple cystitis, the therapeutic results were rated as excellent in 3 cases, and as good in 3 cases, with an efficacy rate of 100%. Regarding 9 cases of chronic urinary tract infections, the results were rated as excellent in 1 case, as good 2 cases and poor in 6 cases. Thus, the efficacy rate in these cases became 33. 3%. Six cases which failed to respond to AB-206 were all diagnosed as having chronic urinary tract infections. In all, the results of treatment were rated as excellent in 4 cases, as good in 5 cases and as poor in 6 cases. The efficacy rate was 60.0%.
2) An inspection of the results as classified by the causative organisms revealed that AB-206 ishighly active against E. coli and that it is also active against Serratia marcescens, Acinetobacter anitratum and Proteus mirabilis.
3) MIC of AB-206 for 26 strains of organisms isolated from 16 out of 22 cases was determined and compared to that of NA and ABPC. It was shown that AB-206 was much more active than NA and ABPC against Serratia marcescens and that in general it was equally or slightly more active against other species of organisms. However, against Enterococcus ABPC was superior to AB-206 and NA.
4) The adverse reactions observed were nausea, dizziness and nausea associated with dizziness in one case each, all of which were mild and transient in nature. With respect to peripheral blood and liver and renal functions, no abnormal findings which could be related to treatment with AB-206 were observed.

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AB-206 was administered to a total of 20 cases of genitourinary infections. The results were as follows.
The subjects consisted of 11 cases of acute cystitis, 5 cases of acute prostatitis, one case of acute pyelonephritis, 2 cases of chronic pyelonephritis, and one case of chronic prostatitis. In all of these cases, AB-206 was found to be effective although the result obtained in one case of acute prostatitis was not so good.
As the causative organisms, E. coli was isolated from 12 cases, Pseudomonas from 3 cases, Entero-bacter from 2 cases, and Klebsiella, Proteus and Staphylococcus epidermidis from one case each. In all but 2 of 3 cases, from which Pseudomonas was isolated, cultures became negative for organisms after treatment with AB-206.
Results of treatment were assessed according to the criteria of UTI for drug efficacy evaluation of AB-206. It was found that with respect to acute cases disappearance of symptoms was observed in 76.5% and improvement in 17.6% of the cases.
In 5.9% of the cases the therapeutic result was assessed as unchanged. Regarding pyuria, disappearance obtained in 76.5% and decrease in 11.8%. In 11.8% of the cases the therapeutic result was rated as unchanged with respect to this symptom. In terms of bacteriuria, conversion into negative was observed in 94.1% and decrease in 5.9% of the cases. Thus, globally the response to treatment with AB-206 was rated as excellent in 70.6%, as good in 23.5% and as poor in 5.9% of the cases.
In the present study AB-206 was administered in a dosage of 750 or 1, 000 mg/day for a period of 7 to 17 days, but in none of the cases any side effects which required discontinuance or reductio n of the dosage of the drug developed.

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AB-206, a new antimicrobial agent, was evaluated clinically on urinary tract infections.
The results obtained were as follows.
1) In 59 cases of acute simple cystitis, the therapeutic results were excellent in 39 cases, good in 10, and poor in 10. The effectiveness rate was 83.1%.
2) In 45 cases of chronic complicated urinary tract infections, consisting of 36 cases of cystitis and 9 cases of pyelonephritis, the therapeutic results were excellent in 4 cases, good in 13, and poor in 28. The effectiveness rate was 37.8%.
3) The MICs of AB-206 against 89 out of 116 isolated organisms were ≤3.13μg/ml, and those against all gram negative rods were ≤50μg/ml.
4) As for the side effects, gastrointestinal disorders were noted in 9 cases.

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AB-206, a new derivative of quinoline, was applied clinically in 32 cases of urinary tract infection.
Twenty-two cases showed good response and others poor, so the effective rate was 68.8% and no remarkable side effect was observed.
Single administration of 4, 000mg AB-206 for male young adult volunteers, 2 in dehydration states and 2 in over-hydration, was performed, and marked side effects, nausea, diarrhea and ataxic gait were observed in all volunteers.

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A new derivative of quinoline, AB-206 which has somewhat related structure to nalidixic acid and showing similar antibacterial spectrum to it with a few exceptions, has been evaluated at our clinics. Fifteen cases of rather stubborn infections established on some predispositions, and 33 cases of simple acute cystitis in female patients were treated with AB-206.
Most of the pathogens were sensitive to nalidixic acid and also to AB-206. Exceptions were one Pseudomonas and one Serratia marcescens strains. A St. epidermidis strain was also resistant. Dosages were 750mg/day to 1500mg/day, divided in three or 1000mg/day, divided in four. Duration of therapy was 7 days in most of the cases, but the longest was 14 days. In some patients in whom severe dizziness was noticed, medication was discontinued within 2 days.
In 15 cases with predispositions, satisfactory result (bacteriological and symptomatological efficacy) was noticed in 4 lower tract infections and in 3 upper tract infections. Poor result was observed in 3 lower tract infections and in 1 upper tract infections, and superinfection was seen in 3 lower tract infections where indwelling cathether was placed. In 1 case prophylactic use of AB-206 during posttransurethral surgery period with indwelling catheter was unsuccessful. The cause of failure was resistance of pathogen in 2 and presence of underlying disease in 2.
In simple acute cystitis cases, 3 failures were seen. The cause of failure was resistance in 1, and suspected underlying disease in 2 (pathogens were sensitive).
As to untoward reaction, dizziness was complained of in 4 cases. The drug was discontinued in 2. In no case abnormal laboratory data were seen.

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AB-206, a new chemotherapeutic agent, was studied both fundamentally and clinically. Results were summarized as follows.
1. MICs of AB-206 for 12 standard strains, 50 urinary E. coli and 25 urinary P. aeruginosa were superior to those of NA.
2. In 27 cases of urinary tract infections, AB-206 was administered at a daily dose of 1g. Satisfactory results were obtained in 15 cases ; 70% in 10 cases of acute simple cystitis, 53% in 15 cases of chronic complicated urinary tract infections. Two cases were dropped out.
3. Side effects were observed in 4 of total 27 cases (nausea, loss of appetite, diarrhea and dizziness). Transient increase of s-GOT was observed in one case.

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AB-206, a new synthetic antibacterial drug with similar chemical structure to nalidixic acid, was evaluated experimentally and clinically in our department. The results were as follows:
1) Concentrations of AB-206 after oral administration of 250 mg were determined in serum and urine of 6 male healthy adult volunteers (3 fasting cases and 3 non-fasting cases). The mean peak concentration in serum was 2.5μg/ml at 1 hour in fasting cases and 2.0μg/ml at 4 hours in non-fasting cases following administration. And the mean urinary recovery during the first 6 hours of administration was 2.2% in fasting cases and 2.6% in non-fasting cases.
2) Thirty-seven patients with urinary tract infections (25 of acute simple cystitis, 10 of chronic complicated infections and 2 of acute complicated cystitis) were given AB-206 250 or 500mg four times a day for 5 days. And the clinical results obtained were excellent in 17 cases (45. 9%), good in 9 cases (24. 3%) and poor in 11 cases (29. 7%).
Three patients exhibited side effects: One with slight epigastralgia, one with dizziness, and one with nausea and headache.
3) It was found that AB-206 was more active than nalidixic acid and piromidic acid against Escherichia coli isolated from urine specimens of patients with urinary tract infections.

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Clinical and bacteriological studies on AB-206 in the field of urology were carried out and the following results were obtained.
1) Clinical results
AB-206 was administered to 16 cases with chronic complicated U. T. I. at dosage of 1g/day for 7 days. Effectiveness was shown excellent in 5, good in 2, poor in 8 and unknown in 1 case (drop-out because of side effect). Efficacy ratio was 46.7% totally.
2) Bacteriological effects
Bacteriological effectiveness of AB-206 was shown eradicated in 4, decreased in 3, unchanged in 8 and unknown in 1 strain. Efficacy ratio was 46.7% totally.
3) Antibacterial activities
MICs were measured in 10 clinical isolated organisms and AB-206 was susceptible to most of all that included NA-and PA-resistant strains. Clinical efficacy was also observed in some of those patients.
4) Side effects
Out of 16 cases, side effect was noted in only 1 case with upper abdominal discomfort. No other side effects and abnormalities of laboratory findings were noted.

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Fundamental and clinical studies on AB-206, a new antimicrobial agent, were carried out and the following results were obtained.
1) AB-206 was proved to show the superior MICs against isolated organisms from urine comparing with NA and PA.
2) AB-206 was orally administered to 23 patients with acute simple cystitis at a daily dose of 750 mg, and the overall clinical efficacy rate was 84. 2% based on the method of evaluation by the UTI-Committee.
3) It was administered to 26 patients with chronic complicated urinary tract infection at a daily dose of 2000 mg, and the overall clinical efficacy rate was 60% by the method of the UTI-Committee.
4) Four patients out of 49, 8. 2%, complained of the side effect, those were drowsiness, dizziness, vertigo and headache. Two cases discontinued taking the drug at the first period of the treatment.
5) No abnormalities were observed when liver and renal function tests and haematological examination were performed before and after the treatment as for the patients administered at a dose of 2000 mg of AB-206.

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AB-206, a new chemotherapeutic agent, was administered to 27 patients with urinary tract infection without underlying disease, and 25 patients except 2 drop-out cases were evaluated clinically.
1. The therapeutic results were excellent in 19 patients, good in 2, poor in 4 in effective rate of 84%. In 22 patients with acute cystitis, the clinical results were excellent in 19, good in 1, poor in 2 in effective rate of 91%.
2. In bacteriological results, there were eradication of the organisms in 20 (80%) out of 25 strains isolated from the urine. Particularly, the effective rate against E. coli was 95%(18 out of 19 strains).
3. Side effects were observed in 2 cases (7. 4%), who complained of anorexia and headache respectively.

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1. Antibacterial activities
The MIC of AB-206 was determined for clinical isolates from the patients with various urinary tract infections. The peak of the MIC values was 0.78μg/ml for E. coli, 3.12μg/ml and 50μg/ml for Klebsiella, 25μg/ml and≥100μg/ml for Pseudomonas aeruginosa, 25μg/ml for Staphylococcus epidermidis and≥50μg/ml for Serratia. AB-206 gave better MIC values by 2-4 grades than NA and by 1-3 grades than PA for E. coli, and by 2 grades than NA and by 2-4 grades than PA for Klebsiella. As for Pseudomonas aeruginosa and Serratia, the compound showed nearly the same distribution of the MIC as NA and PA. It was inferior to NA and PA by 1 grade for Staphylococcus epidermidis.
2. Serum levels and urinary recovery rate
AB-206 was orally given to 2 healthy male adults at a time of non-fasting in a single dose of 250 mg. The serum levels peaked at 2.9μ/ml after 2 hours. The levels gradually fell with the lapse of time, reaching under the determinable limit after 6 hours. The urinary levels reached a peak at 31.8μ/ml after 2-4 hours. The value at 6-8 hours was 1.53μ/ml. The urinary recovery rate during the first 8 hours averaged 3.12%. The serum levels and urinary recovery rate were also determined in 3 other healthy male adults who were given 250 mg of AB-206 4 times a day for 14 days. The serum levels reached a peak of less than 4.60μ/ml on days 1 and 14 without showing any tendency of retention. Comparison of one-hour values on individual days revealed no significant differences. The urinary levels and urinary recovery rate were nearly equal in all the 3 adults, averaging 4.7% on day 1 and 4.3% on day 14.
3. Clinical evaluation
AB-206 was tried in 103 cases of various urinary infections. Its therapeutic effect was estimated as excellent in 70 cases, good in 18 cases and poor in 15 cases. The efficacy rate was 85. 4%. For the group of 82 cases with simple urinary tract infection, the therapeutic effect was excellent in 58 cases, good in 14 cases and poor in 10 cases, and the efficacy rate was 87.8%. For the group of 21 cases with complicated urinary tract infection, the therapeutic effect was excellent in 12 cases, good in 4 cases and poor in 5 cases, and the efficacy rate was 76.2%.
4. Side effec
Only 4 (3.8%) out of the 103 cases treated with AB-206 complained of mild gastric disorder. No cases showed any unusual finding in the hepatic and renal function tests and of hematological tests conducted. No evidence of retention in the blood was seen with the drug continuously administered at 250 mg 4 times a day for 14 days.

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AB-206, a new oral chemotherapeutic agent developed recently in Japan, has been evaluated fundamentally and clinically on urinary tract infections.
1) Minimal inhibitory concentration of AB-206 was determined in 130 strains isolated from urinary tract infections by the plate dilution method. In 10⁸ inoculum size, many strains of E. coli and Proteus mirabilis were inhibited at 1. 56 μg/ml or less. Most strains of Pseudomonas and Serratia were resistant to 50μg/ml of AB-206. Antibacterial activities of AB-206 against clinically isolated E. coli, Proteus mirabilis, Proteus vulgaris, Pseudomonas and Serratia were rather stronger than nalidixic acid.2) Serum and urinary levels of AB-206 250 mg p. o. were determined in one volunteer with nomal renal function. The peak of serum level of AB-206 was 7. 2μg/ml, at 1 hour after oral administraion. The recovery rate from urine for 6 hours was 2.4%.
3) Thirty-eight patients with urinary tract infections were treated with AB-206 at oral dose of 1.0-2.0 g per day.
Clinical results of 25 patients were as follows:
(a) Of 9 with acute simple cystitis, 6 were rated excellent, 2 good and 1 poor.
(b) Of 4 with chronic simple cystitis, 2 were rated excellent and 2 poor.
(c) Of 6 with chronic complicated cystitis, 2 were rated excellent, 1 good and 3 poor.
(d) Of 6 with chronic complicated pyelonephritis, all were rated poor.
4) Gastric discomfort was observed in three cases and diarrhea in one case. The treatment was discontinued in only one case of vertigo. A temporary elevation of GOT was observed in one case.
5) The results suggest that AB-206 is effective and safe in the treatment of urinary tract infections, especially simple infection.

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Clinical studies were made on AB-206 in 55 patients suffering from urinary tract infection, but in only 3 patients administration of AB-206 had to be discontinued due to side effect.
AB-206 was administrated orally at the dosage of 1 or 1. 5 g for 7 days.
Results were excellent in 23 (44. 2%), good in 9 (17. 3%), fair in 7 (13. 5%) and poor in 13 (25.0%) of the 52 cases.
Bacteriological results were eradicated in 26 (50. 0%), decreased in 12 (23. 1%). and unchanged in 14 (26. 9%) of the 52 strains.
As for side effects, gastro-intestinal symptoms, heartburn and obdormition in the extremities or the mouth were observed in 9 cases of this series, in 3 cases of them AB-206 was discontinued.

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1. AB-206 was tried in 21 cases being treated or hospitalized for established urinary tract infections in the department of Urology of Kyushu University Hospital or Shinkokura Hospital.
2. Of 14 cases with acute simple cystitis, 8 cases received 750 mg of the compound a day in 3 divided doses, 3 cases received 1, 000 mg a day in 4 divided doses, 1 case received 2, 000 mg a day in 4 divided doses, and 2 cases received 2, 000 mg a day in 4 divided doses for 4 days after the first consultation and 1, 000 mg a day in 4 divided doses for the following 4 days. One case with acute simple pyelonephritis received 2, 000 mg of the compound in 4 divided doses on the first day of treatment, 1, 000 mg in 4 divided doses on the second day, and 750 mg in 3 divided doses on the third day. Of 6 cases with chronic complicated urinary tract infection, 5 cases received 1, 500 mg of the compound a day in 3 divided doses, and 1 case of 2, 000 mg a day in 4 divided doses.
3. For the group of 15 cases with acute simple urinary tract infections, the therapeutic effect proved excellent in 13 cases, and poor in 2 cases (efficacy rate 86. 6%). For the group of chronic complicated urinary tract infection, the therapeutic effect proved excellent, good and poor in 2 cases each (efficacy rate 66. 6%).
4. Side effects were seen in 3 cases. One case complained of gastric discomfort and another case complained of nausea at every dose, but administration of the compound was continued. The other case complained of gastralgia and dizziness at every dose, and the dose was reduced. As the patient had no complete retreat of the symptom, administration was discontinued after 3 days of trial. Anyway, those symptoms disappeared immediately after discontinuation of administration without needing any special treatment.

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AB-206, one of the analogues of nalidixic acid, has been developed by Taisho Pharmaceutical Co. Ltd. and Sumitomo Chemical Industrial Co. Ltd. in Japan. MICs of AB-206 against 166 strains of bacteria isolated from patients with urinary tract infections including Staphylococcus, E. coli, Klebsiella, Citrobacter, Enterobacter, Proteus spp. and Pseudomonas aeruginosa were measured by agar dilution method.
A peak of sensitivity of the drug against Pseudomonas aeruginosa ranged from 6.25 to 12.5 μg/ml. MICs of the drug against E. coli and other bacteria were shown to be more sensitive than that of nalidixic acid.
Serum level of the drug after 500 mg oral administration in a healthy adult volunteer demonstrated 2.5μg/ml 5 hours later with the highest level. The highest urine level was obtained 2 to 4 hours after the adiministration, however total recovery in the urine by 6 hours reached to 2.5 to 4% with oral administration of 250 mg and 500 mg.
AB-206 was given to 26 cases of acute simple bacterial cystitis in female, 3 cases of acute pyelonephritis and 11 cases of chronic complicated cystitis. Overall clinical efficacy was proved at 92. 3% in acute simple cystitis and 100% in acute pyelonephritis according to criteria for clinical evaluation of antimicrobial agent on acute simple U. T. I. On the other hand, 45. 5% of overall clinical efficacy was obtained according to criteria for clinical evaluation of antimicrobial agent on chronic complicated U. T. I. in Japan. Pyrosis and taste bitter were transiently complained by a case, but no other side effect was noticed by the remainder. Elevation of GOT and GPT was found in a case after prostatectomy.

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Laboratory and clinical studies on AB-206, a new chemotherapeutic agent, were carried out and following results were obtained.
1) Serum levels and urinary excretion of AB-206 were measured in 6 patients without renal and hepatic damages.
The peak values of serum concentration were 10-1.5μg/ml and 11.0-4.6, μg/ml respectively after an oral administration of 250 and 500mg of AB-206.
It was not constant when the peak values of serum concentration were obtained, but dose-response relationships were observed.
The peak values of urinary concentrations were 40-100μg/ml, and urinary recovery rates until 6 hours were 4.4-3.8%.
2) AB-206 was given to 32 patients with various infections at a dose of 250-500mg twice or four times a day.
Isolated organisms were mostly E. coli and other Enterobacteriaceae.
The bacteriological effects were good in 20 cases, poor in 5 cases and unknown in 7 cases.
The clinical effects were good in 23 cases, fair in 5 cases, poor in 2 cases and unknown in 2 cases.
Out of 6 patients with chronic bronchitis, 5 patients were clinically improved.
For side effects, G. I. discomfort appeared in 6 patients, and fatigue and paresthesia of left foot appeared in 1 case combined with α-methyl-dopa.
No abnormality was observed on laboratory findings.

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AB-206 was used in the treatment of various infections listed below with the following results: AB-206 was found to be effective in 1 case of acute pharyngitis, 7 out of 11 cases of acute bronchitis, 1 case each of chronic bronchitis and acute pneumonia, 19 out of 21 cases of acute colitis, 2 cases of acute cystitis, 4 out of 7 cases of acute pyelonephritis, and 2 cases of chronic pyelonephritis, while it was ineffective for chronic cystitis. As a whole, 37 out of a total of 47 cases responded to AB-206, giving an efficacy rate of 79%.
When these results were inspected by the causative organisms isolated, AB-206 was active against 5 of 7 strains of E. coli, 2 of 3 strains of Klebsiella and 1 strain each of Pseudomonas and Enterobacter.
As the side effects, in 1 case dizziness developed and in another case dizziness, nausea and malaise appeared. Laboratory findings revealed abnormalities of liver functions in 2 cases and those of the renal functions in 1 case.

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During experimental studies and clinical trials with AB-206 the following results were obtained:
1. Antibacterial activity
The antibacterial activity of AB-206 against clinical isolated Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa (50 strains each) and Serratia marcescens (12 strains) was examined. Range of minimal inhibitory concentrations was ≤ 0.2-25μg/ml against E. coli, ≤ 0.2-≥100 μg/ml against K. pneumoniae, 0.78-≥100 μg/ml against P. aeruginosa and ≤ 0.2-12.5μg/ml against S. marcescens. The antibacterial activity of AB-206 was much stronger than nalidixic acid (NA) and pipemidic acid (PPA) against E. coli, K. pneumoniae and S. marcescens, and it was much stronger against NA resistant strains and PPA resistant strains of P. aeruginosa.
2. Serum levels
In three healthy adults, 2 hours after a single oral administration of 500 mg of AB-206, peak levels of 2.9-5.4μg/ml were reached. Six hours after administration, the levels decreased to 0.3μg/ml or less. The serum levels obtained by AB-206 were almost comparable to those obtained by 1000 mg of PPA.
3. Cinical results
To nine patients, eight with urinary tract infections and one with food poisoning with Salmonella typhimurium, AB-206 was administered with daily dose of 0.75-2.0 g for 3-14 days. Response to therapy were “excellent” in 2, “good” in 5 and “poor” in 3 cases. Our investigation upon the side effects from AB-206 revealed only dizziness and eruption, which were recovered promptly after the cessation of AB-206 therapy.

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Some experimental and clinical studies on a new synthetic antibacterial agent AB-206 were performed and the following results were obtained.
1) The MIC values of various gram-negative bacilli isolated from clinical material were higher by two to four times for pipemidic acid than for AB-206 in a majority of strains.
MIC values were higher by two to four times when an original overnight broth culture was used as an inoculum than those when its 100-fold dilution was used.
2) In rats with liver dysfunctions due to CCl₄, in particular in those with cirrhosis, it is considered that the metabolism of AB-206 into M-1 and glucuronide of AB-206 and M-1 is depressed when compared to normal rats.
3) In the clinical field, AB-206 was administered to 9 cases of urinary tract infections. The effect of this drug was evaluated as good in 4 cases, as poor in 3 cases and undecided in 2 cases. In one case which was receiving hemo-dialysis on account of renal insufficiency, an elevation in sGOT, sGPT and Al-P was observed following administration of AB-206. However, recovery ensued after cessation of this drug. Although definitive conclusion cannot be drawn, the possibility that AB-206 may be involved in the abnormal elevation cannot be denied.

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Phase I clinical trial of a new chemotherapeutic agent, AB-206 was investigated by administering orally 250 mg and 500 mg of this agent to healthy volunteers and the results were as follows:
i) Relatively high serum levels of AB-206 and the dose response of serum levels among these two doses were observed. Mean serum levels in fasting volunteers were higher than those in non-fasting ones.
ii) Urinary recovery rates of this agent were low (1.5-2.9%), but due to the very potent antibacterial activity, these urinary levels seemed to be sufficient to exert the therapeutic effect on urinary infections.
iii) Neither abnormal values of clinical tests nor subjective and objective signs after administration of this agent were found in total 24 volunteers.

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A total of 24 cases of upper respiratory tract infections were treated with AB-206 in a dosage of 1g/day (250 mg × 4) for 3 to 8 days with following results:
Out of 20 cases of acute pharyngitis, the therapeutic results were rated as excellent in 4 cases, as good in 11 cases, as fair in 3 cases and as poor in 2 cases. Among 3 cases of acute tonsillitis, one case each was evaluated as excellent, as good and as poor, respectively. In one case of acute bronchitis, the response to AB-206 was rated as good. On the whole, an efficacy rate of 87% could be obtained.
As the adverse reactions to AB-206, anorexia, stomatitis and a slight elevation of transaminase occurred in one case each. However, each of these symptoms disappeared following discontinuance of AB-206. From these results AB-206 appears to be a valuable drug in the treatment of upper respiratory tract infections.

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1) Antibacterial activity
MICs against 17 strains of E. coli were under 0.4μg/ml in all of them and more powerful than that of NA and cephalosporin derivatives. MICs against 5 strains of Klebsiella pneumoniae were under 0.78μg/ml. Three of 5 strains of Serratia marcescens were sensitive to AB-206.
2) Clinical results
The results showed to be effective in all of 7 cases of acute pyelonephritis and ineffective in 1 case of Salmonella enteritis.
No side effects were observed in this series.

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We clinically tried AB-206 for treatment of infections in the field of internal medicine, and obtained the following results.
1) AB-206 showed a stronger antibacterial activity by 2-3 stages than NA against clinical isolates of E. coli and Proteus.
2) AB-206 was clinically tried in a total of 30 cases consisting of 15 cases of urinary tract infection, 12 cases of pulmonary infection, 1 case of cholecystitis and 2 cases of colitis. The therapeutic effect was excellent in 9 cases and good in 8 cases, and the efficacy rate was 56. 7%.
3) Side-effects were seen in 3 cases, 1 of whom complained of headache, and the other 2 cases complained of alimentary disturbances such as nausea, vomiting and anorexia. Administration was immediately interrupted in 1 case, while it was switched over to a different drug in the other 2 cases after it was continued for a while.
Treatment was not associated with anything unusual in laboratory findings which could apparently be attributed to AB-206.
It may thus be presumed that the compound has advantages over the existing reference drug in the respects of antibacterial activity and others, and that it will become an effective chemotherapeutic agent, if it is used in cases properly chosen.

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Antibacterial activities and clinical effects of AB-206, a new chemotherapeutic agent, were investigated and the results were as follows:
1. Antibacterial activity of AB-206 against clinically isolated bacteria and the distribution of susceptibility to their strains were studied. The peaks of distribution of susceptibility were 6.25μg/ml in Staphylococcus aureus, 0.39μg/ml in E. coli, 0.78μg/ml in Klebsiella, 0.39μg/ml in Proteus sp., and 25μg/ml in Pseudomonas aeruginosa, tested by small inoculum size.
Compared with the antibacterial activity of pipemidic acid, that of AB-206 was more potent on gram-negative bacteria except for P. aeruginosa.
2. A total of 8 patients with bacterial infections, including 1 case of acute cystitis, 4 cases of chronic cystitis, 2 cases of chronic pyelonephritis and 1 case of bronchiectasis with infection, underwent treatment with AB-206. The drug was administered orally for 2-27 days at doses of 1-2g/ day. The clinical effects were excellent in 2 cases, good in 3 cases, fair in 1 case and poor in 2 cases. As side effect, temporary elevation of GOT and GPT was observed in 1 case.

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Clinical studies on AB-206, a new broad antibacterial spectrum quinoline derivative, were carried out and the following results were obtained:
43 patients with respiratory tract infectious diseases were treated with AB-206 at 1g 4 th a day by oral administration; 3 cases of acute bronchitis, 8 of pneumonia, 2 of lung abscess, one of panbronchiolitis, 21 of chronic bronchitis and 9 cases of bronchiectasis.
Out of 10 cases of pneumonia and lung abscess, clinical excellent and good response was observed in 70% and 4 cases out of 9 acute exacerbated chronic respiratory tract infectious disease revealed good result. Good correlation was also observed between these clinical results and bacteriological effect on the organism detected from sputum specimens. In this respect, these effects are favorably comparable with some reliable studies reported previously.
In 20 cases of chronic course type of infectious chronic bronchitis and bronchiectasis, good response was observed in 15.0%. This poor effect will be due to low degree of infectious findings, advanced and prolonged chronic bronchial inflammation.
As side effect, each one case complained of nausea, appetiteloss and epigastrial discomfort in slight degree and slight elevation of GOT was observed in 2 cases.

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AB-206, a newly synthesized antibacterial chemotherapeutic, was studied on its clinical effectiveness, and the following results were obtained.
Six patients (acute bronchitis 2, chronic bronchitis 2, and U. T. I. 2) were treated orally with AB-206 (1, 500mg-2, 250mg/day). Good results were obtained in four and poor in two of the cases. No marked side effects were observed throughout the clinical trials.

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Laboratory and clinical investigations were performed on AB-206 and the results obtained were as follows;
1) Sensitivity of clinically isolated strains to AB-206 was tested by agar plate dilution method and compared with that of nalidixic acid (NA). The minimum inhibitory concentrations of AB-206 against 50 strains of E. coli and 43 strains of Proteus mirabilis were 0.39 to 25μg/ml and 0.39 to 12.5μg/ml respectively. Thirty-six out of 50 strains of Serratia marcescens and 45 out of 50 strains of Klebsiella pneumoniae were inhibited in the range of 0.39 to 12.5μg/ml of AB-206.
The antibacterial activity of AB-206 against most of clinical isolates was found to be superior to that of NA.
2) Serum concentrations of AB-206 1 hour after 250mg and 500mg of oral administration reachedpeak and the levels ranged from 3.0 to 3.6μg/ml and 12.0 to 20.0μg/ml respectively.
The concentration of AB-206 in sputum was 3.2μg/ml.
3) Four of five patients with chronic respiratory tract infections treated with AB-206 showed effective clinical result. No side effect was observed in all patients.

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Fundamental and clinical studies on AB-206, a new antimicrobial agent, were carried out and the following results were obtained:
1. Antimicrobial activity:
Minimal inhibitory concentrations (MICs) of AB-206 against 22 standard strains which had been subcultured in our department and 664 strains (Staphylococcus aureus 54, Salmonella 36, Citrobacter freundii 38, C. diversus 24, C. amalonatica 10, E. coli 53, Shigella 45, Klebsiella aerogenes 53, Enterobacter aerogenes 54, Ent. cloacae 54, Serratia marcescens 54, Proteus vulgaris 13, Pr. mirabilis 41, Pr. rettgeri 22, Pr. inconstans 16, Morganella morganii 43, Pseudomonas aeruginosa 54) isolated from the various clinical materials were determined in comparison with those of nalidixic acid (NA). MICs of AB-206 were 2 to 4 times lower than those of NA in almost all bacteria.
2. Absorption and excretion in man:
Three healthy male adults were given 500 mg of AB-206 orally at fasting time and the peak serum levels were 5.3 to 6.25μg/ml 1 to 2 hours after administration. Two healthy male adults were also given 500 mg of AB-206 orally after meal and the peak serum levels were 3.8 to 6.25μg/ml 2 to 4 hours afterwards.
A 54 years old female patient with chronic bronchitis was administered 500 mg of AB-206 after meal and its peak level of the drug was 5.8μg/ml 4 hours after medication. Urinary recovery rates within 6 hours were 5.4 to 7.8%.
3. Clinical effect:
Five patients with pulmonary infections (Bronchopneumonia 2, Bronchiectasis 1, Chronic bronchitis 1, Acute bronchitis 1) were treated by 1, 500 mg of AB-206 per day. Clinical and bacteriological effectiveness was poor in all five cases.
4. Adverse reaction:
Subjective and objective symptoms and hematological, biochemical data and renal function were checked up after administration of AB-206. No side effect was observed.

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Laboratory and clinical studies on AB-206 were performed and the following results were obtained.
1. The antibacterial activities of AB-206 against clinically isolated gram-negative respiratory pathogens were given as under.
1) The MICs against Haemophilus infinenzae were in the range from 0.2μg/ml to 3.13μg/ml. The peak MIC was at the value of 0.39μg/ml.
2) The MICs against Escherichia coli ranged from 0.39μg/ml to 0.78μg/ml. The peak MIC was at the value of 0.78μg/ml.
3) The MICs against Klebsiella pneumoniae focussed on the value of 0.78μg/ml.
2. The tissue concentrations of AB-206 were estimated in rats after one time of oral administration of 50mg/kg. The peak levels were attained at two hours after the administration. The tissue levels at the peak were the highest in serum, followed in descending order by lung and kidney.
However, no drug was detected in liver.
3. Serum and sputum concentrations and urinary excretion of AB-206 were studied in a male patient with C. P. E. and chronic bronchitis. The drug was not detected in serum until two hours after the administration and revealed the highest value at four hours after the administration. The urinary recovery rate was 2%. The ratio of sputum peak level to serum peak level was 8%.
4. AB-206 was administered to one case of respiratory tract infection and six cases of urinary tract infection. It was effective in all cases.
5. As an apparent side effect of AB-206, a slight elevation of GOT was observed in one case.

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AB-206 was administered at 1 or 2 g for 5 days to the patients of bacterial infections of intestinaltube and the results were as follows;
1) Clinical results were effective in 2 of 3 cases of bacillary dysentery, and ineffective in 1. Causative bacteria were eliminated in 3 cases.
2) Clinical results were effective in 2 of 2 cases of Salmonella enteritis. Causative bacteria were eliminated in 1 of 2 cases.
3) In 12 cases which causative organisms were not able to be detected, AB-206 was effective in all cases of these dysentery-like diseases.
4) AB-206 concentrations in feces demonstrated 2.4-67.7μg/g.
5) Side effect was not observed subjectively and objectively in all cases.

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Clinical effect of AB-206, a new synthetic agent which is active against Gram-negative bacteria and some of the Gram-positive bacteria, was carried out with the following results.
1) AB-206 was orally administered to one patient of dysentery, three patients of salmonellosis and other entero-colitis at dosis of 2g/day with good clinical effects.
2) No abnormalities were observed in hematological and biochemical examinations after serial administration of AB-206 to patients for 5 days.
3) The minimal inhibitory concentrations of AB-206 against Shigella strains were 0.20-0.78μg/ ml, and those against Salmonella strains were 0.20-0.78μg/ml.

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AB-206 was administered to 8 cases of infections of the digestive organs.
Because of the scarcity of the number of cases included, no definitive conclusion could be drawn. However, we may be justified to interprete the therapeutic results obtained in one case of dysentery, one case found to be a carrier of Salmonella, and 2 cases of vibrio infection as effective.
As the side effects, stomach discomfort was noted after administration of AB-206 in one case only.

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We tested antibacterial activity of AB-206 and also carried out a clinical study on it. The results obtained are as follows.
1) Antibacterial spectrum
AB-206 was found to possess high antibacterial activity against Staphylococcus among gram-positive organisms and E. coli, Klebsiella pneumoniae and Proteus among gram-negative organisms.
2) Sensitivity of clinically isolated organisms
The antibacterial activity of AB-206 was superior to PPA and NA against Staphylococcus aureus, E. coli, Klebsiella pneumoniae and Proteus in particular Proteus mirabilis. Against Pseudomonas aeruginosa, AB-206 was equally active with PPA and more active than NA.
3) Clinical results
AB-206 was administered to 29 cases of infections encountered in the surgical field and found effective in 24 cases and ineffective in 5 cases, the efficacy rate being 82.7%. As the side effects, only one case complained of nausea and vertigo.

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Fundamental and clinical studies on AB-206 were investigated and following results were obtained.
(1) Antibacterial activity
The sensitivity of AB-206, PPA and NA was examined in E. coli, Klebsiella and Ps. aeruginosa. In comparison with PPA and NA, AB-206 was more effective to E. coli and Klebsiella, whilst it was not so effective to Ps. aeruginosa.
(2) Absorption and excretion
AB-206 (250mg) was administered once at fasting in 3 healthy adults, and blood level and urinary excretion were examined. Peak blood level on average was 2.8μg/ml at 1 hour and recovery from urine within 6 hours was 2.8%.
(3) AB-206 was administered to 5 patients with surgical infections and the results were excellent in 1 case, good in 2, fair in 1 and poor in 1. No particular side effects were observed.

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Oral AB-206 was tried on 36 cases with various infectious diseases in the field of surgery, and the clinical therapeutic effects obtained were as follows: excellent in 8 cases, good in 14, fair in 6, poor in 7 and unknown in 1, while therapeutic effectiveness was considerably remarked in 11 of 14 cases (79%) with soft tissue infections. However, eradication of clinical isolates was documented in 16 of 30 cases (53.3%).
Both of serum level and urinary excretion were studied by means of bioassay method on healthy adult male volunteers after oral dose of AB-206.

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AB-206, a new chemotherapeutic agent, was clinically applied to 17 patients with postoperative infection.
In 2 cases, serum levels, biliary concentrations and urinary recovery rates were examined.
Results were obtained as follows.
1) Clinical application
Effectiveness of AB-206 was Excellent for 3 cases, Good for 11 cases and Poor for 3 cases.
The effective rate was 82.4%.
Elevations of GOT, GPT and BUN, and elevation of BUN were observed in each one case.
2) Absorption and excretion
Serum levels after 500 mg of AB-206 were orally administered were investigated, reaching the peak value of 10.0μg/ml at 3-4 hrs.
Biliary concentrations after 500 mg of AB-206 were orally administered were investigated, reaching the peak value of 41.7μg/ml at 5-6 hrs.
Urinary recovery rates in 2 cases were 4.86 and 9. 74%.

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