An attempt was made to study absorption and excretion of amphotericin B in healthy male adult volunteers and patients with chronic pulmonary diseases such as tuberculosis or mycosis following a single oral administration in the form of tablet and syrup.
For determination of amphotericin B concentration in body fluid and feces, the turbidity method was employed by using Candida albicans Shibuya strain with sensitivity ranging from 0.01 to 0.2 mcg/ml. Fecal samples for determination were prepared by homogenizing the feces collected during every 24 hours by the addition of phosphate buffer of pH 6. 2. Thereafter, the samples were lyophilized and then extracted overnight by adding 100% dimethylsulfoxide. In vitro recovery rate of amphotericin B from positive control was 75%.
In the above volunteers and patients, antifungal activity of amphotericin B failed to be traced in serum samples during the course of experiment following a single oral administration at a dose of 35 mg/kg body weight. No traces of the activity were detected except in two of fifteen urine samples collected during the first 24 hours after the administration.
During the four-day period following the administration of amphotericin B to the volunteers and patients, the rate of recovery in feces reached 28%-78% and 15%-86% respectively. It was learned, however, that the excretion takes place mostly within the first three days following the administration. These results seem to give an evidence to the clinical efficacy of amphotericin B in suppressing an overgrowth of Candida and other yeasts in the gastrointestinal tract and subsequent infections.
During the study, no side reaction was noticed whatsoever could be attributable to the drug or necessitated discontinuation of administration.

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Influence of various factors on antibacterial activity of lincomycin (LCM) and clindamycin (CLDM), population of natural resistant mutants and development of resistance to these drugs were studied. The effects of oral administration of LCM and CLDM on anaerobic fecal flora of four healthy adults of 25 to 43 years old were also examined.
In comparison of activities of two drugs on four media, many strains used were inhibited by similar minimum inhibitory concentration on four media.
Antibacterial activities of both drugs were stronger on GAM agar adjusted to pH 9 than on that adjusted to pH 6.
The effect of carbon dioxide on the sensitivity of anaerobes to LCM was studied. The values MIC of LCM for many anaerobes except Veillonella, Fusobacterium were two to eight times higher, when tested in nitrogen plus 10% or 50% carbon dioxide, than the values obtained in pure nitrogen.
P. variabilis (10⁹/ml viable cell) was streaked on GAM agar plates containing 50 mcg/ml LCM or 25 mcg/ml CLDM and natural resistant mutants were obtained.
F. varium (10⁸/ml viable cell) was streaked on GAM agar plates containing 100 mcg/ml LCM or CLDM and natural resistant mutants were obtained, but these mutants were unable to grow on GAM agar plates containing 12.5 mcg/ml of LCM.
After 18 to 30 serial cultures in GAM semisolid media containing drugs, the MIC against P. variabilis increased from 0.39 mcg/ml to 25 mcg/ml.
After 8 serial cultures in GAM semisolid media containing CLDM, the MIC of F. varium to CLDM increased from 1.56 to 100 mcg/ml and also the MIC of this organisms to LCM increased from 3.13 mcg/ml to 100 mcg/ml after 18 serial cultures with this drug.
When administrated orally both LCM and CLDM, this administration showed little bacterial effect on anaerobic fecal flora of four healthy adults.

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Susceptibilities of 145 strains of anaerobic bacteria to SF 837, a new macrolide antibiotic developed by Research Laboratory of Meiji Seika, were examined.
Many strains of Peptococcus and Peptostreptococcus were sensitive to this drug, while strains of Veillonella were relatively resistant.
SF 837 showed strong activity to Bacteroides and little activity to Fusobacterium so that this drug may be useful to differentiate genera among gram negative anaerobic rods.

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Effects of bromelain on absorption, distribution and excretion of josamycin were investigated in the normal and experimentally infectious rat.
When given orally, josamycin was slowly absorbed from upper part of small intestine. Its marked. affinity of tissue was observed, and it was slowly excreted in the urine. When combined with bromelain, peaks of its plasma and organ concentrations were observed earlier than the control and it was excreted more rapidly. Affinity of kidney and spleen for josamycin was slightly greater than that of liver in view of biological activity, while affinity of liver was greater when isotopically measured. Bromelain accelerated the permeability of intestine to josamycin, and increased its passage into external fluid from intestine at alkaline pH.
It is concluded therefore that bromelain accelerates absorption of josamycin and elevates early blood. and organ levels.

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Antitumor effects of 5-FU by oral administration were studied using several experimental tumors and compared with the effects when given intravenously.
1. When about two times dose of 5-FU was given orally, its antitumor effect was comparable to the effect when given intravenously in Leukemia L-1210, solid tumors of Sarcoma 180 and YOSHIDA sarcoma.
2. Oral administration of 5-FU daily for 3 weeks inhibited markedly the growth of mammary carcinoma KSP-1.
3. The concentration of 5-FU in the tumor when given orally was lower about two times than that when given intravenously, and the level of 5-FU concentration in the tumor remained longer than the blood level of 5-FU.
4. The leucocyte depression caused by the oral administration of 5-FU was weaker than that by the intravenous administration at the dose of the approximately same antitumor effect.
In the both routes the depression of the increase in the body weight was observed, but slightly stronger in the oral administration.

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The characteristics of biliary excretion of cefazolin (CEZ), cephalothin (CET) and cephaloridine (CER) were studied6 preliminarily in rats. Based on these results, a suitable method of CEZ administration was evaluated for the treatment of bile tract infection in humans.
The relationship between dose and biliary levels of these cephalosporins was investigated in rats following an intramuscular injection. The bile levels of CEZ and CET increased as the dose increased, while CER did not show such response. Bile levels of CEZ and CET were higher than serum levels at the dose of 10-80mg/kg, whereas in CER administration serum levels were higher than bile levels.
Comparison was made, to obtain the highest bile level, among various administration routes of cephalosporins at the same dose.
Based on the results obtained from the studies in rats, a crossover study was carried out to compare the bile levels of CEZ and CER in 5 patients of cholethiasis with T-tube drainage of common bile duct after intravenous injection of 1g single dose. The peak concentration of CEZ was 0.85-21 mcg/ml and that of CER was 0.55-3. 9 mcg/ml.
In another crossover study of CEZ and CET in 5 patients after intravenous injection of 3g single dose, the peak concentration of CEZ in bile was 35.5-270 mcg/ml and that of CET was 0.3-64 mcg/ml. The sufficient bile levels of CEZ for the therapy of bile tract infection were obtained with the intravenous dose of 3g.

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From the laboratory and clinical studies on propionylmaridomycin (PMDM), a new macrolide antibiotic, the following results were obtained.
1) Antibacterial spectrum
The antibacterial activity of PMDM was similar to that of each known macrolide antibiotic such as leucomycin and josamycin, and this antibiotic did not induce a resistance.
The minimum inhibitory concentrations (MIC) of PMDM were 0.39-3.13 mcg/ml against Staph. aureus. The MIC of PMDM for Streptococci group was found to be similar to that of this antibiotic against Staph. aureus. But PMDM was ineffective against gram-negative enteric bacteria.
2) The sensitivity distribution for 54 clinical isolates of Staph. aureus
The sensitivity distribution was studied on PMDM, 4 ″-deacyl-PMDM and other macrolide antibiotics. The sensitivity distribution of PMDM was found to be similar to that of josamycin and mydecamycin.
The standard curve at pH 7.0 was similar to that at pH 8. 0, but the standard curve was different between that in human serum and in monitrol serum to one tube on antibacterial activity.
3) Serum level and urinary excretion
Serum level and urinary excretion of PMDM were studied by the cup method with S. lutea ATCC 9341 as a standard organism. Serum level of PMDM in healthy adults given a single oral dose of 400 mg demonstrated peak level of 0.46 mcg/ml respectively two hours after administration, and serum level at six hours after administration was 0.27 mcg/ml.
Concentration of PMDM in urine demonstrated peak level of 24.5 mcg/ml two hours after administration. The cumulative urinary recovery of PMDM was 0.55% for 8 hours after administration.
4) Tissue concentration
After oral administration of 200 mg/kg PMDM to SD strain rats, the highest tissue concentration of PMDM was found in lungs, followed by liver, muscle, serum, kidneys, heart and brain.
5) Metabolism
The metabolism was studied by thin layer chromatography and bioautography. The administered PMDM was metabolized to 4″ -deacyl-PMDM, maridomycin, 4Prime;-deacyl-maridomycin and unknown metabolites.
6) Clinical results Twenty-nine patients with infections in the field of surgery were treated with PMDM, which was effective in 19 patients (65.5%).
No noticeable side effects were found.

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The clinical courses have been analyzed on 90 adult patients with gram-negative rod bacteremia. The yearly frequency rate of the disease has tended to increase. The highest rate was seen in 1972 at 4. 1 episodes per 1, 000 admissions to Chiba University Hospital.
Mortality of the overall patients was 49%. Shock was seen in 38% of them. The mortality was analyzed from severity of underlying disease and accompanying of shock. Mortality of the patients having nonfatal underlying disease without shock was least, 17%, whereas that of the patients accompanying ultimately fatal underlying disease with shock was 78%. None of the patients of rapidly fatal underlying disease survived.
The most common organisms isolated from the bacteremia was E. coli, followed by Klebsiella, Pseudomonas, and Proteus, in order. E. coli was isolated more frequently from the patients with nonfatal underlying disease, whereas Pseudomonas was detected more frequently in the cases with fatal underlying disease, and associated with the highest mortality. Polymicrobial bacteremia was seen in 10% of the patients. The most common source of the bacteremia was urinary tract, and followed by biliary tract. The species of the isolated organisms was different in character following the portal of entry, hospital service, category of underlying disease.
All but four patients had high fever. Leukocytosis was not seen in 32% of the patients without hematologic disease and they were mostly elderly persons. Instrumentation of urinary tract, immunosuppressive agents, hematologic disease, biliary and hepatic disease, diabetes mellitus, and neoplastic disease appeared to be chief predisposing factors of the bacteremia. More than a half of the patients acquired the bacteremia in the hospital. All isolated gram-negative rods, except Bacteroides, were susceptible to gentamicin in vitro.

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Bactericidal activities of amoxycillin and ampicillin were examined and compared by using Escherichia coli as test organisms. Amoxycillin showed a more rapid bactericidal action than ampicillin in experiment of the effect on the growth curve with biophotometer and viable cell counts. Observation of the bactericidal picture with phase-contrast microscope confirmed the rapid bactericidal action of amoxycillin and revealed that amoxycillin destroys organisms in different manner from ampicillin. These suggest some difference in the action mode between amoxycillin and ampicillin.
Amoxycillin ^{1, 2)} is a semi-synthetic penicillin for oral use developed in 1970 at Beecham Research Laboratories in England. Like ampicillin, it has broad antibacterial spectrum.
Amoxycillin has such a chemical structure as a hydroxyl group is introduced into benzene nucleus of ampicillin at para position. It is stable in acid, like ampicillin, and absorbed well, blood concentration of amoxycillin after oral administration in a certain dose being about twice as high as that of ampicillin administered in as much dose^3-6) .
The effect of amoxycillin against gram-positive and-negative organisms is nearly equal with that of ampicillin ^{1, 2)} . According to ROLINSON et al. ²⁾ , there was no difference in bactericidal activities between amoxycillin and ampicillin. We found, however, in detailed investigation of the activities of amoxycillin and ampicillin against Escherichia coli strains through biophotometer and by counting of viable cells, that amoxycillin produces greater bactericidal effect than ampicillin in an initial stage. The experiments and results are described below.

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Mycobacterium tuberculosis strain H 37 Rv has two phenotypes of TUM-N resistance; one low resistance-type and another high resistance-type. The former is resistant to 200 μg/ml level of TUM-N, CPM and VM. The latter is resistant to more than 1, 000 μg/ml level of TUM-N, CPM, VM, LVM and KM. Both types are susceptible to other antituberculous agents.
VM-resistant strains of the organism are resistant to VM, CPM and TUM-N. KM-highly resistant strains are resistant to KM, LVM and CPM, and KM-lowly resistant strains are resistant to only KM. CPM-resistant strains are resistant to CPM, VM, TUM-N and LVM. LVM-resistant strains are resistant to LVM, VM, CPM and KM. SM-resistant strains are susceptible to other agents.

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