Pharmacokinetic and clinical studies on aztreonam in the perinatal period in obstetrics and gynecology

Pharmacokinetic and clinical studies on aztreonam (AZT) in the perinatal period in obstetrics and gynecology were performed with the following results. 1. Concentrations of AZT in maternal serum, umbilical cord serum, amniotic fluid and neonatal serum were determined after 1 hour intravenous drip infusion of 1 g. The maternal serum concentration was 32.2 micrograms/ml at 26 minutes after administration, gradually decreasing thereafter to 13.2 micrograms/ml at 2 hours 33 minutes, 4.9 micrograms/ml at 3 hours 21 minutes and 2.9 micrograms/ml at 5 hours 3 minutes. Umbilical cord serum concentration was 17.0 micrograms/ml at 36 minutes after drip infusion and still remained at 4.0-16.1 micrograms/ml at 5 hours after administration. Amniotic fluid concentration was 9.9 micrograms/ml at 3 hours 21 minutes after drip infusion and showed 3.3 micrograms/ml at 16 hours 26 minutes after administration. Most of the maximum serum concentrations of newborns between 3 to 24 hours after delivery were not detectable, with only one case with 2.2 micrograms/ml at 9 hours after delivery. 2. AZT 1 or 2 g x 2/day was given by intravenous drip infusion to 12 cases of perinatal infections in obstetrics and gynecology for 5 to 8 days. Clinical efficacies were evaluated as excellent in 8 cases, effective in 2 and not effective in 2 with 83.3% efficacy rate. With respect to side effects, minor degree of urticaria was observed in 1 case. Another case showed a transient elevations of GOT, GPT and Al-P in laboratory tests.     

Pharmacokinetic and clinical studies of flomoxef in perinatal period

Pharmacokinetic and clinical studies of flomoxef (FMOX) in perinatal period were carried out and the following results were obtained. 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid were determined subsequently to intravenous injection (4 cases) and intravenous drip infusion method (20 cases) of 1 g FMOX. Maternal serum levels were similar to those of healthy adults, and peak levels of umbilical cord sera and amniotic fluids were 12.0 micrograms/ml and 12.05 micrograms/ml, respectively, using intravenous drip infusion. The levels in amniotic fluids were higher than those in umbilical cord sera at 2 hours after treatment in either administration method. Parameters T 1/2 (beta) and AUC were 1.05 hours and 74.1 micrograms.hr/ml, respectively. 2. In the treatment of 4 cases with perinatal infection and in prophylaxis cases, clinical efficacies of FMOX were all good with 1 g twice daily treatment using intravenous drip infusion. No side effects nor abnormal laboratory test values due to the drug were observed in any cases. These results indicate that single intravenous drip infusion of FMOX 1-2 g twice daily is effective for the treatment and the prophylaxis of perinatal infections.     

Pharmacokinetic and clinical studies on flomoxef in perinatal period

Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period were carried out. The results are summarized as follows. 1. The concentration of FMOX in umbilical cord serum was about 10 micrograms/ml in about 30 minutes after 1 g one shot intravenous injection. Amniotic fluid concentration was 7 micrograms/ml in 41 minutes after administration. By 1 hour intravenous drip infusion, FMOX concentration in umbilical cord serum was about 5 micrograms/ml in 2-3 hours after administration. Amniotic fluid concentration of about 20 micrograms/ml was found in 1 case. 2. FMOX 1-2 g x 2-3/day was given by intravenous drip infusion to 7 cases of perinatal infection for 4-26 days. Clinical efficacies were evaluated a good for all cases. Neither side effect nor abnormal laboratory test value was observed. Consequently, FMOX was considered to be highly effective and safe for its clinical use in perinatal period infections.     

Pharmacokinetic and clinical studies on aztreonam in the perinatal period

Pharmacokinetic and clinical studies of aztreonam (AZT) in perinatal infections in the field of obstetrics and gynecology were performed with the following results. 1. At one shot intravenous injection, 1 g AZT showed rapid distribution to the umbilical-cord serum with concentrations higher than 15 micrograms/ml in 1 hour 36 minutes after injection and higher 10 micrograms/ml even in 4 hours 30 minutes after injection. Significant difference in concentrations was not observed between arterial serum sample and venous serum sample of the umbilical-cord in a single subject. The concentration in the amniotic fluid reached a level higher 10 micrograms/ml in 3 hours 37 minutes after injection. 2. Distribution into milk reached a concentration between less than 0.4 micrograms/ml to 1.0 micrograms/ml by 6 hours after administration. 3. AZT 1 g x 2/day was given by intravenous drip infusion to 4 cases of perinatal infection in obstetrics and gynecology for 5 to 9 days. Clinically, AZT was effective for all the cases. Neither side effect nor abnormal laboratory value was observed. Consequently, AZT was considered to be highly effective and safe for its clinical use in the parturition and the puerperium.     

Pharmacokinetic and clinical studies on aztreonam in perinatal period

Pharmacokinetic and clinical studies were carried out on aztreonam (AZT), a monobactam antibiotic with a high activity against Gram-negative bacteria. The results obtained are summarized as follows: 1. Following 2 g bolus intravenous injection, transfers of AZT to umbilical cord serum and amniotic fluid were found to be satisfactory. AZT level in amniotic fluid was higher than 1 micrograms/ml at 40 minutes after administration and it was at 3.7 micrograms/ml in 23.5 hours. 2. In the treatment of 9 patients with perinatal infections, clinical efficacies of AZT were judged excellent in 3 cases and good in 6 cases. 3. No side effects and abnormal laboratory findings due to the drug were observed in any case. These results indicate that AZT may be a useful antibiotic for the treatment of perinatal infections.     

Pharmacokinetic and clinical studies on flomoxef in the perinatal period in obstetrics and gynecology

Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period in obstetrics and gynecology were performed and the results obtained are summarized as follows: 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid were determined after intravenous injection of 1 g. The maternal serum concentration was 41.9 micrograms/ml at 16 minutes after administration, and gradually decreased thereafter to 1.36 micrograms/ml at 5 hours 19 minutes. The concentration of FMOX in umbilical cord serum was 17.5 micrograms/ml at 16 minutes after administration, then gradually decreased thereafter, was slightly higher than that in maternal serum after approx. 3 hours and was 2.88 micrograms/ml at 5 hours 19 minutes. The amniotic fluid concentration was 0.31 micrograms/ml at 16 minutes after administration, increased to 7.85-15.8 micrograms/ml at approx. 3 hours, and gradually decreased while maintaining relatively high levels. 2. One or two grams of FMOX were given by intravenous drip infusion twice daily to 17 patients with perinatal infections for 5 to 7 days. Clinical efficacies were evaluated as excellent in 7 cases and good in 10, suggesting that FMOX was effective in all cases. No subjective side effects were observed in any of the 17 patients. As to abnormal laboratory findings, a minor degree of elevation of GPT was observed in 1 patient and that of GOT.GPT in 1. No other abnormal changes in laboratory examinations were observed. Considering the above results, we conclude that FMOX is a useful antibiotic in perinatal infections.     

Pharmacokinetic and clinical studies of ceftazidime in perinatal period

Pharmacokinetic studies and clinical evaluations of ceftazidime (CAZ) were carried out in perinatal mothers and infants, and following results were obtained. The CAZ was promptly absorbed after intravenous injection or intravenous drip infusion in pregnant women, producing dose-related peak serum levels. Placental transference to the fetus was good. After intravenous injection or intravenous drip infusion of 1.0-2.0 g of CAZ, drug concentration in umbilical serum and amniotic fluid exceeded MICs of CAZ against main pathogenic organisms. Levels of CAZ in umbilical serum ranged 0.2-15.6 micrograms/ml after 1.0 g intravenous injection or intravenous drip infusion, and 0.7-27.2 micrograms/ml after 2.0 g intravenous injection, and those in amniotic fluid were 1.4-21.3 micrograms/ml after 1.0 g administration and 2.0-27.0 micrograms/ml after 2.0 g administration. According to the above results, it is possible to successfully prevent or treat perinatal infections by twice a day administration of CAZ at 1.0-2.0 g/dose. Clinically, CAZ was effective in the treatment of perinatal infections and the prophylaxis of intrauterine amniotic infection without any side effect. Moreover, newborn infants delivered from mothers receiving CAZ treatment did not have any abnormalities in laboratory test. The penetration of CAZ into mother's milk was low, thus the transfer of CAZ from milk to newborn infants should be low. The above results demonstrated that CAZ is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.     

Pharmacokinetics and clinical evaluations on aztreonam in perinatal infections in obstetrics and gynecology. A study of aztreonam in the perinatal co-research group

Pharmacokinetics and clinical studies on an injectable monobactam antibiotic aztreonam (AZT), were carried out in perinatal infections in obstetrics and gynecology and the obtained results are summarized as follows. 1. Pharmacokinetic study (1) Upon one-shot intravenous injection of AZT 1 g before delivery, maternal serum concentration of AZT was 89.0 micrograms/ml immediately after the injection and a half-life (T 1/2) of 0.96 hour was observed. Umbilical-cord serum concentration showed a peak value of 16.5 micrograms/ml at 1.26 hours after the injection and gradually decreased with a T 1/2 of 1.91 hours. The transfer into amniotic fluid was observed and the peak value of AZT in amniotic fluid reached 12.9 micrograms/ml at 5.57 hours after the injection and slowly decreased thereafter with a T 1/2 of 4.42 hours. Transfer and disappearance in one-shot 2 g intravenous injection and 1 g intravenous drip infusion (1 hour) of AZT were very similar to the results obtained with the one-shot 1 g intravenous injection. (2) The residual serum concentration in neonates after one-shot 1 g intravenous injection of AZT to the mother was almost below the detectable limit. Transfer of AZT into milk was scarcely recognized. 2. Clinical studies (1) AZT was injected to 47 cases with various perinatal infections and it was more than "effective" in 45 cases with an efficacy rate of 95.7%. Also, all the 12 cases to which AZT was administered for prophylaxis of infections showed prophylactic effect. Bacterial eradication was obtained with 25 strains out of 29 aerobic Gram-negative bacteria, but 1 strain "persisted" and for 3 strains results were "unknown", hence an eradication rate of 96.2% was obtained. However, AZT treatment resulted in a little lower eradication rate against Gram-positive bacteria. (2) One case (1.3%) of minor degree of urticaria was found as a side effect, and one case each of eosinophilia and elevation of GOT, GPT and Al-P was observed as abnormal laboratory value. From the above results of pharmacokinetics and clinical evaluation, it has been concluded that AZT is a useful and highly safe drug in various perinatal infections and prophylaxis.     

Studies on aztreonam in the perinatal period

Pharmacokinetic, bacteriological and clinical studies on aztreonam (AZT) in the perinatal period were carried out with the following summary of the results. Antibacterial effects of AZT on bacterial growth of Escherichia coli (MIC 12.5 micrograms/ml) and Pseudomonas aeruginosa (MIC 50 micrograms/ml) in amniotic fluid were determined and it was found that the activity of AZT is enhanced in amniotic fluid. AZT rapidly penetrated into tissues and sera of pregnant women upon intravenous (i.v.) injection and its maternal serum concentrations reached their peak levels shortly after the injection. Placental penetration of AZT to the fetus was good and, after single i.v. injection of 1 g, the concentrations of AZT in the umbilical cord serum and amniotic fluid exceeded MICs against major Gram-negative bacilli. These results indicate that single i.v. injection of AZT 1 g twice a day is effective for the treatment and prophylaxis of perinatal infections. Injection of AZT for the treatment of puerperal infections showed excellent clinical effectiveness with 100% eradication of aerobic Gram-negative rods. No side-effect was observed in any case. All of the results suggested clinical usefulness of AZT in the perinatal period.     

Fundamental and clinical studies on aztreonam in obstetrics and gynecology

Fundamental and clinical studies on gynecological use of aztreonam (AZT), a new monobactam, were performed with following results. Following the intravenous administration of 1 g dose of AZT, the transfer of AZT to pelvic dead space exudate was good, in which the concentration of that was 14.9 micrograms/ml (2 hours), 15.3 micrograms/ml (3 hours) after injection. The transfer of AZT to serum of umbilical cord and amniotic fluid was excellent. In a clinical trial, AZT was given to 5 patients with obstetric and gynecological infections. The clinical efficacy was evaluated as excellent in 1 case and good in the other 4 cases. No adverse effects were observed in any of the patients treated with AZT.     

Experimental and clinical studies on latamoxef during the perinatal period

Fundamental and clinical studies on the perinatal use of latamoxef (LMOX) were performed, with the following results. Concentration of LMOX was examined in maternal serum, umbilical cord serum and amniotic fluid after intravenous administration of 2 g dose. Data were analyzed by the simulation curves using the two-compartment model. The peak level of LMOX in maternal serum was 218.4 micrograms/ml and half-life of the beta-phase was 1.9 hours. The peak levels of LMOX in umbilical cord serum and amniotic fluid were 37.4 micrograms/ml (1.4 hours) and 27.5 micrograms/ml (8.9 hours) after administration. The concentration of LMOX in amniotic fluid decreased in amount after the peak, but it still remained 21.9 micrograms/ml (16 hours) after administration. Above these results, it was concluded that the transfer of LMOX to umbilical cord serum and to amniotic fluid was sufficient. In clinical use, LMOX was administered to 30 pregnant patients with premature rupture of membrane. It showed excellent efficacy in preventing perinatal infection. Seven patients with perinatal infections were treated with LMOX and all of them had excellent efficacy. No side effects were observed in any of the cases studied.     

Pharmacokinetic studies on cefsulodin in perinatal period

Pharmacokinetic studies on cefsulodin (CFS) were carried out in perinatal mothers and infants. The results obtained are summarized as follows. 1. CFS was promptly absorbed upon intravenous drip infusion in pregnant women, producing dose-related peak serum levels. Placental transference to the fetus occurred quickly and at high levels. Upon intravenous drip infusion of 1-2 g of CFS, drug concentration of the cord blood and amniotic fluid exceeded MICs of clinically isolated strains of Pseudomonas aeruginosa. These levels in cord blood ranged 3.3-16.9 micrograms/ml upon 1 g intravenous drip infusion and 0.8-21.6 micrograms/ml upon 2 g intravenous drip infusion, and in amniotic fluid they were 1.3-15.6 micrograms/ml upon 1 g administration and 5.5-17.9 micrograms/ml upon 2 g administration. The drug was transferred into newborn infant through placenta, showing no tendency to accumulate. According to the above results, it appears possible to successfully prevent or treat perinatal infections through administration of the dose of 1-2 g twice daily. 2. Moreover, newborn infants delivered from mothers receiving CFS administration showed no laboratory test abnormalities. 3. The penetration of CFS into mother's milk occurred at low levels, and the transference from milk to newborn infants appeared to occur at even low levels. The above results have demonstrated that CFS is a clinically useful antibiotic for prophylaxis and treatment of perinatal Pseudomonas infections.     

Pharmacokinetic study of aztreonam transfer from mother to fetus

Aztreonam (AZT) was administered to 73 cases and its usefulness and safety were evaluated upon review of the transfer of the drug into maternal blood, umbilical cord blood and amniotic fluid. The result obtained are summarized as follows. 1. AZT was intravenously administered by single injection to obtain actual data. Based on the data, theoretical changes of drug concentrations in serum in mother were reviewed according to the lapse of time. Drug concentration in maternal blood showed its peak immediately after administration and gradually decreased thereafter. Umbilical cord blood concentration showed a lower peak, which was reached with a slight delay to the Tmax for maternal blood concentration, then decreased. The decrease, however, was more moderate than the decrease in maternal blood concentration and, according to the theoretical values, umbilical cord blood concentration was higher than maternal blood concentration at 2.23 or 2.24 hours after administration. AZT concentrations in amniotic fluid slowly increased after administration and were higher than umbilical cord blood concentrations at 1.68, 1.73 hours after administration, higher than maternal blood concentrations at 1.82, 1.85 hours after administration, and they reached their peak somewhat later. Subsequently, high concentrations of AZT in amniotic fluid were maintained for a long time. The result suggests that AZT is useful for prophylaxis and treatment of amniotic fluid infections. 2. Theoretical values were analyzed by applying two-compartment model and three-compartment model to the actually-measured values, and each parameter was compared. T 1/2 of AZT concentrations in maternal blood and in umbilical cord were 1.29 hours, 1.29 hours, 2.14 hours, 2.00 hours; Cmax 187.09 micrograms/ml, 184.15 micrograms/ml, 30.63 micrograms/ml, 30.66 micrograms/ml and AUC 153.25 micrograms.hr/ml, 153.40 micrograms.hr/ml, 123.19 micrograms.hr/ml, 123.09 micrograms.hr/ml respectively showing approximate values. Cmax values of AZT in amniotic fluid were 47.08 micrograms/ml, 47.74 micrograms/ml; AUC 948.03 micrograms.hr/ml, 1,028.70 micrograms.hr/ml also showing approximate values. However, volume of distribution of umbilical cord blood and amniotic fluid showed a difference according to compartment model. 3. It was considered from the above results that application of only two-compartment open model would make analysis possible when only T 1/2, Cmax and AUC values must be measured for mother-to-fetal transfer of a drug. 4. No subjective and objective side effects nor abnormal laboratory values were observed in any of these cases (both mothers and fetuses).     

Fundamental and clinical studies on ceftazidime in the perinatal period

Fundamental and clinical studies were carried out on ceftazidime (CAZ) in the perinatal period, and the results obtained were summarized below. Following bolus intravenous injection of CAZ 2 g, maternal serum concentrations of CAZ were as high as 145.3 +/- 17.2 micrograms/ml (mean +/- S.D.) at about 10 minutes, and then gradually decreased to 46.7 micrograms/ml at 2 hours, 5.31 micrograms/ml at 5 hours and 4 minutes, and 1.54 micrograms/ml at 11 hours and 10 minutes. The CAZ was detected in umbilical cord serum immediately after the administration, and concentrations were 31.0 +/- 1.54 micrograms/ml at about 10 minutes. Although the concentrations gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and later and was 3.00 micrograms/ml at 11 hours and 10 minutes. The CAZ was detected in amniotic fluid a little later than in umbilical cord serum, and concentrations of CAZ in amniotic fluid were as low as 1.50 +/- 0.67 micrograms/ml at about 10 minutes after the administration. Concentrations then gradually increased to 12.8 micrograms/ml at 2 hours and 26.5 micrograms/ml at 5 hours and 4 minutes, and even at 11 hours and 10 minutes, they were as high as 14.2 micrograms/ml. The above results demonstrated that the transfer of CAZ through placental barrier was very rapid and satisfactory. Also, CAZ showed good transfer into amniotic fluid, as well as sufficient retention, and was considered to be an effective antibiotic for prophylaxis of both fetal infections and amniotic fluid infections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placental transfer and pharmacokinetic parameters of flomoxef during the perinatal period

Flomoxef (FMOX), a new oxacephem with low MIC values against not only Gram-negative bacilli (GNB) but also against Gram-positive cocci (GPC), was evaluated for its transfer into fetus, amniotic fluid, maternal milk, spinal fluid and urine during the perinatal period following a single intravenous drip infusion at a dose of 1 g for 30 minutes. The results obtained are summarized below. 1. High concentrations of FMOX were demonstrated in maternal serum, umbilical arterial serum and amniotic fluid with Cmax values of 48.0, 10.99 and 10.20 micrograms/ml, respectively. 2. Maternal urinary excretion rate was 65.4% in the first 6 hours after administration. 3. In contrast, maternal milk and spinal fluid levels were lower than 3 and 0.20 micrograms/ml, respectively. These results showed a good placental transfer of FMOX, which is very useful for various perinatal infections. No adverse effects were observed in mothers and neonates during the course of this study.     

Pharmacokinetic and clinical studies on ceftizoxime in the perinatal period

Pharmacokinetic and clinical studies were carried out on the use of ceftizoxime (CZX) in the perinatal period. The results obtained are summarized below. 1. Mean maternal serum concentrations of CZX reached 57.3 micrograms/ml at about 15 minutes after a single intravenous injection of CZX 1 g and then gradually decreased to 13.1 micrograms/ml in 1 hour and 55 minutes, 3.59 micrograms/ml in 4 hours and 20 minutes and 0.11 microgram/ml in 17 hours and 51 minutes. CZX in umbilical cord serum was at detectable concentrations soon after administration and peaked to 23.5 micrograms/ml in 32 minutes. Although the concentrations in umbilical cord serum gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and more after an injection and was 0.41 microgram/ml at 17 hours and 51 minutes. The CZX in amniotic fluid became detectable a little later than CZX in umbilical cord serum. The concentration of CZX in amniotic fluid was below 1.00 microgram/ml at 30 minutes after administration. Concentrations then gradually increased to 21.3 micrograms/ml in 1 hour and 55 minutes and, even in 17 hours and 51 minutes, they were as high as 9.44 micrograms/ml. 2. In the clinical evaluation, CZX was given to a total of 7 cases, i.e., 1 of amnionitis, 2 of puerperal endometritis, 1 of puerperal fever, and 3 of pyelonephritis. The treatment showed satisfactory results, i.e. excellent result was obtained in 1 case, good in 5 and poor in 1 with an clinical efficacy rate of 85.7%. Microbiological examinations resulted in the isolation of 5 bacterial strains of 4 species and 1 fungal strain from 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic and clinical studies on ceftriaxone in the perinatal period

Ceftriaxone (CTRX), a new cephalosporin antibiotic, was studied for its pharmacokinetic features and clinical efficacy in the perinatal period and the obtained results are summarized below. 1. Following a one shot intravenous injection of 1 g of CTRX into each of 29 parturient women, CTRX levels were between 4.5 and 19.5 micrograms/ml at 6 hours postdose and between 4.5 and 4.7 micrograms/ml at 24 hours postdose in the amniotic fluid and between 11.7 and 22.7 micrograms/ml at 6 hours postdose and between 4.5 and 4.7 micrograms/ml at 24 hours postdose in the umbilical cord serum. It was shown that CTRX was maintained there at high levels for a long time and the transfer of CTRX into the umbilical cord serum was better than that of other antibiotics. 2. Following a one shot intravenous injection of 1 g of CTRX into each of 12 cases of puerpera, CTRX was detected in the mother's milk until 10 hours postdose, though at a very low level averaging 0.32 to 0.79 microgram/ml. It was considered, however, that CTRX affected little infants through the mother's milk. 3. CTRX was evaluated to be very effective in 2, effective in 5 and ineffective in 1, of 8 cases of infections during the perinatal period. From the above results, CTRX appeared to be effective against infections during the perinatal period.     

A study of clinical application of cefotaxime in the perinatal period

Pharmacokinetic studies of cefotaxime (CTX) were carried out in perinatal mothers and infants. CTX was promptly absorbed after intravenous injection, intravenous drip infusion and intramuscular injection in pregnant women, producing dose-related peak blood levels. Placental passage to the fetus was favorable. After intravenous injection, intravenous drip infusion and intramuscular injection of 500--1,000 mg of CTX, drug concentrations of the cord blood, amniotic fluid and fetal blood exceeded MICs of the main pathogenic organisms. By administration of this dose 1 to 2 times daily it is possible to successfully prevent or treat uterine infections. Passage of CTX into the milk of lactating mothers was minimal, suggesting that only minute quantities can possibly be transferred from the milk to newborn infants. Absorption of CTX in neonatal infants was prompt. The peak blood levels of 47.9 micrograms/ml were attained 15--30 minutes after intravenous injection of 20 mg/kg. The half-life ranged from 2.4--5.56 hours, depending on the number of days postpartus. CTX was effective in the prophylaxis and therapy of perinatal uterine infections.     

Fundamental and clinical studies of aztreonam in the field of pediatric

The fundamental and clinical studies of aztreonam (AZT) were performed. The results were as follows: The MICs of AZT for E. coli and Salmonella sp. which were recently isolated in the pediatric field were less than 0.78 micrograms/ml. AZT also was effective against ABPC/PIPC-resistant bacteria. The MIC of AZT for V. parahaemolyticus was less than 1.56 micrograms/ml. The peak serum levels of AZT which were occurred just after the 1 hour drip infusion of 10-30 mg/kg were 60.5-136.8 micrograms/ml, and at 6 hours after infusion the serum levels were 1.3-6.1 micrograms/ml; therefore, the dose response was proved. The mean half-lives (T 1/2) were between 1.21 and 1.36 hours. The excretion rates in urine up to 6 hours after intravenous drip infusion were between 32.7 and 77.5%. The ratio of the cerebrospinal fluid concentration to serum in the child with purulent meningitis was 3.5% at 1 hour after the intravenous injection at the dose of 69 mg/kg, and the ratios of the subdural fluid levels to serum were 31.3-37.5%. The levels of AZT into the feces by the multiple dosage were 0-840 micrograms/g. Twenty-five pediatric patients with acute infections had been treated by intravenous injection or drip infusion at the doses of 49-120 mg/kg/day (almost 50-100 mg/kg/day) for 4 to 13 days. The efficacy rate of excellent + good was 84% and that of excellent + good + fair was 96%. The efficacy rate of excellent + good was 100% in all cases with upper/lower respiratory tract infection, bronchopneumonia, and acute urinary tract infection caused by Gram-negative rods. The clinical efficacy was observed in all cases with acute bacterial enteritis. Although AZT was clinically effective against Salmonella enteritis, bacteriological efficacy on the causative organisms was not observed in some cases. Although AZT was bacteriologically effective in 1 patient with typhoid, it did not alleviated fever. AZT showed activity to 9 strains isolated from the culture of throat swab, urine and feces. No side effects were clinically observed in all cases, while slight elevations of laboratory findings were observed in 4 cases.     

Pharmacokinetic and clinical studies of ceftizoxime in the perinatal period. The Chemotherapy Research Group for Mothers and Children

Pharmacokinetic and clinical studies of ceftizoxime (CZX) in the perinatal period gave the following results: 1. Peak concentrations of CZX in the maternal serum, umbilical cord serum and amniotic fluid in mothers after one intravenous injection of 1 g were, respectively, 70.2 micrograms/ml at 0 hour; 15.7 micrograms/ml at 0.5 hour; and 10-30 micrograms/ml at 3-6 hours. Concentrations of CZX in the neonatal serum were 0.87-13.5 micrograms/ml during 6-14 hours after parturition. The mean concentration of CZX in the milk in 1-8 hours after injection was less than 0.32-0.52 microgram/ml. 2. Good or excellent clinical efficacy was obtained in 28 of the 29 patients with perinatal infections, with an efficacy rate of 96.6%. Prophylactic effectiveness was obtained in 14 of the 15 patients, with an efficacy rate of 93.3%. 3. No side effects were observed in 44 cases. GOT and GPT values increased slightly in 1 patient. No abnormal values in total serum bilirubin or other parameters were found in any neonates after parturition. 4. The above results suggest that CZX is safe and effective for the treatment and prophylaxis of infection in the perinatal period.