Ceftriaxone (CTRX) was clinically evaluated and its pharmacokinetics studied in neonates. The results obtained are summarized below.
1. Blood levels of CTRX at 8 to 12 hours after intravenous injection with a single dose of 10 to 20mg/kg ranged from 14.9 to 32.8μg/ml, while T 1/2 ranged from 8.2 to 24.8 hours.
2. Blood levels of CTRX at 11 hours after the completion of drip infusion which lasted one hour with a dose level 10 to 20mg/kg, ranged from 10.6 to 25.0μg/ml, while T 1/2 was 5.4 to 22.8 hours.
3. Multiple intravenous administrations were given to premature infants, but blood levels did not show evidence of drug accumulation.
4. Urinary excretion in 6 hours after an intravenous injection or a drip infusion with 10-20mg/kg of CTRX ranged from 13.8 to 58.5% of the dosage.
5. The subjects in this study were 9 neonates with suspected sepsis, pneumonia, Staphylococcus epidermidis or Staphylococcus aureus infections (sepsis, staphylococcal scalded skin syndrome, pneumonia), acute bronchitis or meconium aspiration syndrome. Efficacies CTRX were excellent or good in all these cases administered in a daily dose of 19.5 to 41.6mg/kg for 4 to 11 days
6. No general side effects or abnormalities were observed in blood count, or hepatic or renal function.

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Ceftriaxone (CTRX) was clinically evaluated and its pharmacokinetics studied in neonates and premature infants, and the results obtained are summarized as follows.
1. Average blood levels of CTRX after intravenous administration of 10mg/kg in 3 neonates with birth weights of 2,500g or more were 45.32mcg/ml at 15 minutes, 28.91mcg/ml at 1 hour, 15.76mcg/ml at 6 hours, and 16.28mcg/ml at 12 hours, and the half-lifew as 9.93 hours. The half1ife in a newly born premature infant (less than 1 day) was 28.90 hours, and in a premature infant 6 days old it was 12.90 hours.
2. Average blood levels after intravenous administration of 20mg/kg to 2 neonates aged 0 and 3 days with birth weights of 2, 500g or more, were 129.7mcg/ml at 15 minutes, 60.94mcg/ml at 1 hour, 32.04mcg/ml at 6 hours, and 24.23mcg/ml at 12 hours, and the half-life as 8.95 hours. The half-life in a newly born premature infant (less than 1 day) was 20.70 hours.
3. Urinary recovery rates of CTRX in 12 hours after intravenous administration of 10 or 20mg/kg to 6 neonates aged 0 to 3 days (including premature infants) ranged from 13.8 to 50.6%.
4. Clinical efficacies of CTRX were excellent or good in 3 of 4 neonates including infants suspected of having infections ( efficacy rate: 75%).
5. As a side effect, diarrhea was noted in 1 case.

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To 39 neonates and premature infants 1 to 28 days old with various bacterial infections or suspected bacterial infections and were nearing cure-stage via ceftriaxone (CTRX) therapy, CTRX 10mg/kg or 20mg/kg was intravenously administered by bolus injection, and the changes in serum concentrations and urinary recovery rates of the drug were examined. Because the number of cases included was small, a comparison study was conducted by classifying them into three groups; less than 4 days old, 4 to 7 days, and 8 days or older, rather than dividing them into groups of neonates and premature infants. Clinical evaluation was conducted in 10 male and 6 female cases 1 to 46 days old, whose diseases comprised 1 case each of purulent meningitis, septicemia, pyothorax, phlegmonous cellulitis, and staphylococcal scalded skin syndrome, plus 5 with bronchopneumonia and 6 with urinary tract infection.
1. Changes in serum concentrations and urinary recovery rates
(1) Intravenous bolus injection of 10mg/kg:
Serum concentrations in all three groups were the highest immediately after the drug administration, ranging from 32.3 to 35.9μg/ml, with no significant differences noted among the groups. The levels gradually declined thereafter in all groups; to 12.7 to 18.3μg/ml at 6 hours and 8.4 to 13.2μg/ml at 12 hours. Averaged blood half-lives of CTRX were 11.3, 8.8, and 17.3 hours. The urinary recovery rates in the first 6 hours in the 3 groups were 31.0, 27.9, and 26.0%, respectively.
(2) Intravenous bolus injection with 20mg/kg:
Serum concentrations were the highest immediately after the drug administration in all 3 groups, ranging from 56.5 to 73.1μg/ml. The levels gradually declined thereafter in all groups, but remained rather high at 17.9 to 21.1μg/ml at 6 hours and 13.2 to 16.8μg/ml at 12 hours. The older the patients were, the shorter the serum half-lives of CTRX were: 25.5 hours in the less than 4 day old group, 11.7 hours in the 4 to 7 day old group, and 10.5 hours in the 8 days or older group. The urinary recovery rates in the first 6 hours in the 3 groups were 25.5, 22.3, and 21.8%, respectively.
2. Clinical results
Clinical evaluation was made in 16 cases. CTRX at 11.9 to 60.0mg/kg/day, was administered once daily or in 2 divided doses, daily. In all cases, including those with presumed severe infections that included 1 case each of purulent meningitis, septicemia and pyothorax, the efficacy was good or excellent. Causative pathogens were bacteriologically identified in 15 cases, including 5 strains of Escherichia coli, 2 of Klebsiella pneumoniae, 5 of Staphylococcus aureus, 2 of Streptococcus pneumoniae, and 1 of Group B Streptococcus, but excluding case No.6 with bronchopneumonia. All of these bacteria were eradicated during the therapy.
3. Side effects
No subjective or objective side effects were observed in any case. Regarding laboratory abnormalities, GOT elevation was noted in only one case, and it was of no clinical significance.

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1. Ten neonates 0 to 28 days old (gestation: 37-42 weeks; birth weight: 2, 160-3, 640g) received 20mg/kg CTRX (8 cases) or 10mg/kg (2 cases) by intravenous bolus injection, while 9 infants 35 days to 9 months old (gestation: 37-43 weeks; birth weight: 2,800-3,560g) received 20mg/kg by intravenous bolus injection, and their blood drug concentrations and urinary drug excretions were examined.
Average blood levels of CTRX in the 20mg/kg dosage group were 114±14.6μg/ml at 30 minutes, 109±12.8μg/ml at 1 hour, 100±12.6μg/ml at 2 hours, 87.9±15.8μg/ml at 4 hours, 72.8±15.3μg/ml at 6 hours, and 50.1±12.3μg/ml at 12 hours in the neonates; and 11320.0 g/ml at 30 minutes, 101±14.7μg/ml at 1 hour, 83.6±9.3μg/ml at 2 hours, 70.3±10.7μg/ml at 4 hours, 56.9±8.6μg/ml at 6 hours, and 35.7±9.2μg/ml at 12 hours in the infants.
Average half-lives of CTRX in blood were 10.3±4.5 hours in the neonates, and 6.6±1.9 hours in the infants.
Average blood concentrations of CTRX in the 10mg/kg dosage neonate group were 63.8±6.0μg/ml at 30 minutes, 57.8±2.5μg/ml at 1 hour, 53.5±0.7μg/ml at 2 hours, 41.8±7.4μg/ml at 4 hours, 32.4±5.9μg/ml at 6 hours, and 20.8±1.1μg/ml at 12 hours, and the half-life was 7.2±0.4 hours.
These results suggest that blood concentrations are apparently dose-related in the neonate period; that the peak levels of the neonate and infant groups were similar (the levels at 30 minutes) not showing a relationship to age, gestation period or to birth weight; and that the higher the age was the shorter the half-life became with the half-life in the one week old group was 1.5 times as long as that in the older infant group. The half-life in the younger infant group, however, was similar to that in the older infant group.
Urinary excretion was examined in 4 neonates and 2 infants. Average urinary recovery rates in 12 hours after intravenous injection were 40.8±8.3% in the neonate group and 44.8±12.8% in the infant group, showing that CTRX is excreted well even in the neonate period.
2. CTRX was administered into 13 neonates with bacterial infections (age: 0-26 days), and the clinical efficacy, bacteriological efficacy, and side effects were examined. In principle, 20mg/kg was given once or twice a day for neonates aged up to 7 days, and twice for those aged 8 days or more.
The clinical efficacies in 5 with acute pneumonia, 3 with acute bronchitis, 2 with acute urinary tract infection, and 1 case each with suspected sepsis, periproctal abscess and staphylococcal scalding skin syndrome were excellent in 9 cases, good in 3 and fair in 1 (efficacy rate: 92.3%).
Concerning bacteriological efficacy, 1 strain each of pathogens Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Haemophilus influenzae, Klebsiella pneumoniae, and 2 strains of Escherichia coli, were all eradicated except S. aureus which was reduced; the eradication rate was 85.7%.
No side effects were noted in any of the cases. As laboratory abnormalities, eosinophilia, thrombocytopenia and elevation of GOT were observed in 1 case each, but these findings were confirmed normal on a follow up retest.
The above results show that CTRX is a useful and safe drug even in the neonate period.

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Following a one shot injection with ceftriaxone (CTRX) 10 mg/kg or 20 mg/kg into 23 neonates (1 to 24 days old) including premature infants, plasma levels of CTRX were measured up to 12 hours post-dose in some cases and up to 72 hours post-dose in others and also urinary levels and urinary recovery rates were determined up to 12 hours post-dose. Furthermore, clinical, bacteriological and infection-prophylactic effects of CTRX were evaluated by the intravenous administration with the mean dose of CTRX of 47.7mg/kg once daily or half the dose twice daily for 9 days on the average into 46 infants (0 to 6 months old) including neonates and premature infants; i. e., 21 cases with actual or suspected bacterial infections for the evaluation of clinical and bacteriological effects and 25 without bacterial infection for the evaluation of prophylactic effects against bacterial infection. The safety of CTRX was evaluated in 53 cases including 7 which were omitted from the efficacy evaluation due to adverse reactions and also in some cases from clinical laboratory parameters. The following is a summary of the results obtained:
1. Following the administration with CTRX 10 mg/kg into each of the neonates 6, 12, 13 and 21 days old (the 21 old one was premature), plasma levels of CTRX in these subjects reached their peaks at 5 minutes post-dose at levels of 59.38, 53.13, 37.50 and 50.00μg/ml, respectively. The peak levels were similar to each other with an exception of the rather low level in the 13 day-old neonate. The plasma half-life times of CTRX in these subjects were 9.762, 7.775, 7.330 and 8.149 hours, respectively: The younger the infant the longer the half-life tended to be except the premature cases. Similarly, the younger the infant the larger the AUC was except for the premature case with the AUC values of 511.169, 324.714, 236.346 and 326.825μg·hr/ml, respec-tively. The Vds were 0.709, 1.004, 1.316 and 0.696 liters, respectively, and the value for 13 day-old neonate was the largest. Urinary levels of CTRX reached between 42.00 and 298.30μg/ml at some time within 12 hours post-dose in any cases. Urinary recovery rates in 12 hours post-dose were 79.98, 52.00, 56.82 and 60.14%, respectively.
2. By the administration of CTRX 20mg/kg to each of subjects in the following 5 age groups; 3 premature infants aged younger than 3 days, 4 neonates aged 4 to 7 days, 3 premature infants aged 4 to 7 days, 5 neonates aged 8 to 28 days and 4 premature infants aged 8 to 28 days, the plasma level reached its peak at 5 minutes post-dose in any of the subjects in any of the groups: Average peak levels in these groups were 83.34, 77.35, 109.39, 95.63 and 100.79μg/ml, respectively. A dose-response relationship was observed between 10mg/kg and 20mg/kg dose levels. Mean plasma half-lives were 15.528, 6.661, 10.546, 9.145 and 10.379 hours, respec-tively thus the younger the infant was, the longer it tended to be except for the group of neo-nates aged 4 to 7 days. Furthermore, half-lives tended to be longer in premature infants than in neonates regardless of age. The mean AUCs were 850.894, 348.329, 639.233, 572.205 and 616.240 pg·hr/ml, respectively, and AUCs in the premature infants younger than 3 day old were the largest. AUCs tended to be larger in premature infants than in neonates regardless of age. Mean Vds were 1.025, 1.676, 1.091, 1.440 and 1.087 liters: Vds tended to be larger in neonates than in premature infants.
Urinary levels of CTRX reached between 34.10 and 782.00μg/ml at some time in 12 hours post-dose. Urinary recovery rates in 12 hours were 23.15, 37.08, 41.64, 28.47 and 27.16%, respec-tively, and the rate in the group of premature infants aged younger than 3 days was the lowest.
3. The clinical efficacy rate was 85.7% in 21 infants with actual or suspected bacterial in-fection.

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Ceftriaxone (CTRX) was studied for its efficacy and safety in 8 cases of infection during the perinatal period; 6 before, and 2 after delivery. The results obtained are recognized as follows:
1. CTRX was administered by intravenous drip infusion at a daily dose between 2 and 4g for 2 to 10 days (a total dose: 4 to 20g) each of 8 cases of infections during the perinatal period; 3 of amniotic fluid infection and 1 each of intrauterine infection, puerperal fever, puerperal wound infection, appendicitis and pyelonephritis. CTRX was evaluated to be very effective in 3, effective in 3 and ineffective in 2, with an efficacy rate of 75%(6/8).
2. Two strains of Enterococcus faecalis and 1 each of Pseudomonas cepacia and Streptococcus intermedius were isolated. All of them were eradicated by the CTRX treatment bacteriologically.
3. No adverse reactions were observed subjectively or objectively. A slight transient elevation of GOT, GPT and Al-P was observed in 1 case. No abnormal sign was observed in neonates.

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Cefbuperazone (CBPZ) was administered to patients with severe infections complicating hematologic diseases to assess its efficacy and safety under such clinical conditions. Primary diseases in this series of 78 cases included; acute leukemia in 41 cases, chronic leukemia in 6 cases, other leukemia in 9 cases, malignant lymphoma in 13 cases, multiple myeloma in 3 cases, aplastic anemia in 5 cases and 1 other case. Types of infection included sepsis; proven or suspected, in 59 cases, pulmonary infection in 8 cases, upper respiratory infection in 5 cases, and other cases. CBPZ was infused by an intravenous drip method at a dosage of 4-8 g daily. Patients' ages ranged from 14 to 85 years.
Clinical response to the CBPZ regimen was excellent in 24 cases, good in 22 cases, fair in 2 cases, and poor in 30 cases. Thus the overall efficacy rate (percentage of cases showing an excellent or good response) was 59.0%. Efficacy rates for individual types of infection were: documented sepsis 16.7%, suspected sepsis 58.5%, lower respiratory infection 62.5%, and upper respiratory infection 100%.
CBPZ also proved to be effective in 61.0% of cases with a neutrophil count of less than 500/mm³ prior to therapy. Side effects encountered were diarrhea in 1 case, gastric discomfort in 1 case and hepatic dysfunction in 5 cases. These side effects, however, were not doserelated, and none were serious.
These results indicate that CBPZ has a high therapeutic efficacy even in patient with compromised immunodefenses.

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We conducted clinical studies on the efficacy and safety of cefbuperazone (CBPZ) on surgical infections with the following results.
1) In evaluable 32 patients, CBPZ was evaluated to be clinically effective in 23 (71.9%) and the efficacy rate was better in those who were administered 4g/day of CBPZ (87.5%, 14/16) than in those who were given 2g/day (57.1%, 8/14).
2) Antibacterial activity of CBPZ was evaluated in 41 isolated bacterial strains. Pathogen eradication rate by bacterial species was 75.6% (31/41). CBPZ exerted excellent antibacterial effects on Escherichia coli (100%, 8/8) and anaerobic bacteria such as Bacteroides (88.9%, 8/9). Resistant bacteria to CBPZ were Enterococcus faecalis and Pseudomonas aeruginosa.
3) No serious side effects were noted in any of the 34 patients who entered in this study. Abnormal laboratory test results were noted in 2 patients (5.9%) and they were transient elevation of transaminases and alkaline phosphatase.
From the results shown above, CBPZ appears to be a highly useful antibiotic for the treatment of surgical infection.

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Cefotetan (CTT), a newly-developed cephamycin antibiotic, has been used widely for the treatment of various infectious diseases because of its excellent antibacterial potency and dynamic transport in vivo. Although the drug transfer to almost every organ, tissue, and body fluid has been studied, only a few reports are available regarding the transfer to lung tissue.
In the present study, 1g of CTT was intravenously injected in a single dose to each of 22 patients subjected to pulmonary resection. Subsequently, its concentrations in blood and lung tissue were measured in sequence. The degree of transfer of the drug to the lung tissue was calculated to evaluate the pharmacodynamics of CTT in vivo. The following results were obtained in this analysis.
1. The T 1/2(β) of the concentration in blood was 4.18 hours, and AUC^0-∞ was 478.7 μg·hr/ml.
2. C_max in the lung tissue was 31.5 μg/g, and Tmax was 0.83 hour, and tissue concentrations decreased in parallel to blood concentrations.
CTT was transferred to the lung tissue to achieve high concentrations following an intravenous administration. Since high concentrations are maintained for a long period of time, this antibiotic is expected to exert an excellent effect in the prevention and the treatment of respiratory infections.

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We investigated the pharmacokinetics of cefmenoxime (CMX) administrated to renal-failure patients undergoing continuous arteriovenous hemofiltration (CAVH). CAVH was carried out with a filter (0.5m²) employing a PAN-50P (hollow fiber type) made of polyacrylonitrile membrane, with a blood flow rate of 100 ml/min and a filtration rate of 1,200 ml/hr.
At 5 and 300 minutes after the CMX administration, the concentrations of CMX in the serum were 126.8 mg/L and 31.5 mg/L, respectively. The T 1/2 β was 3.55 hours. In 300 minutes after the administration of CMX, the total amount of CMX contained in the filtrate corresponded to 11.6% of the administered dose.

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