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 studies of transferred concentration of piperacillin into maternal serum, umbilical cord serum and amniotic fluid

In order to evaluate the clinical efficacy of piperacillin (PIPC) in the obstetrical field, 1 g of PIPC was intravenously administered to 45 normal term gravidas and PIPC concentrations in maternal serum, umbilical cord serum and amniotic fluid were determined. Fifty-three samples of maternal serum, 45 samples of umbilical cord serum and 44 samples of amniotic fluid were obtained at amniotomy and delivery. The results of these studies are summarized as follows. 1. Mean biological half life of PIPC in maternal serum administered to term gravidas was 61.43 minutes. 2. Placental transfer of PIPC concentration into umbilical cord serum was about 71% of maternal serum concentration after 1 hour. 3. There was no prominent difference in the PIPC concentrations of the amniotic fluid between the ruptured and unruptured cases. Fast transfer of PIPC into the amniotic fluid was recognized, such as 1 case was already raised to 4.3 micrograms/ml of PIPC in the amniotic fluid at 1 hour after administration. 4. The maternal serum and amniotic fluid concentration had a contrary relationship, and crossed each other at ca. 5 micrograms/ml of concentration after 2 hours and 50 minutes. Over a period of 6 hours and 20 minutes, the amniotic fluid concentration gradually increased.     

Clinical trial and basic study on the tissue transfer of cefminox

Cefminox (CMNX, MT-141) was studied both fundamentally and clinically with following results: In the treatment of 3 cases of Bartholin's abscess, 2 cases of pyometra, and 1 case each of bartholinitis, inflammation of the pelvic dead space, retroperitoneal abscess and pelvic peritonitis, CMNX was administered at a dosage of 1 g. The global clinical results were rated as good in 9 cases. From these findings it is considered that CMNX is promising as an antibiotic with extremely high efficacy for infections of the field of obstetrics and gynecology. Furthermore, since in none of our cases side effects or laboratory abnormalities were observed, CMNX is considered to be a drug with high efficacy and safety. In 5 cases received 1 g of CMNX intravenously, concentrations of the drug in the serum and tissues of internal genital organs were determined. CMNX was maintained at concentrations higher than 20 micrograms/ml for the serum and 10 micrograms/g for each tissue studied. In the pelvic dead space exudate 10 to 20 micrograms/ml of the drug was still detected even at 8 hours after the administration. These results obtained by our fundamental study support the efficacy of CMNX demonstrated in the clinical part of our study.     

Fundamental and clinical studies on cefminox in the field of obstetrics and gynecology

Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied both fundamentally and clinically with following results. In 33 cases undergone total hysterectomy and adnexectomy, 1 g of CMNX was administered intravenously by the drip infusion route over 1 hour and changes in drug concentration in the venous blood and uterine arterial blood as well as in various uterine tissues including endometrium, myometrium, cervix uteri, portio vaginalis, oviduct and ovary were studied. In addition, in 3 cases also received 1 g of CMNX over 1 hour by the drip infusion route, changes in the concentration of CMNX in the pelvic dead space exudate were investigated. In each tissue studied, the drug concentration higher than 40 micrograms/g was attained at 20 minutes after completion of drip infusion, showing good transfer of CMNX. In the pelvic dead space exudate, the peak concentration of 24.7 micrograms/ml appeared at 4 hours after completion of drip infusion and at 12 hours still a concentration of 4.5 micrograms/ml was maintained. In the treatment of 15 cases of obstetrical and gynecological infections, CMNX was used. In all of the cases treated, clinical results better than good were obtained, with excellent results in 2 cases and good results in 13 cases. In none of the cases side effects or laboratory abnormalities were observed. From these results CMNX is considered to be a useful drug for the treatment of various infections in the field of obstetrics and gynecology.     

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.     

Pharmacokinetics and clinical studies on cefminox in the field of obstetrics and gynecology

Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and the penetration of CMNX into pelvic dead space exudate were good. The mean peak serum level after single intravenous injection was 190.8 micrograms/ml. The level in pelvic dead space exudate reached a peak of 36.6 micrograms/ml 4 hours after an intravenous injection of 1 g and 6.5 micrograms/ml after 12 hours, thus the level over MIC against main pathogenic organisms was maintained for a long time. CMNX was administered against gyneco-obstetrical infections such as intrauterine, intrapelvic, adnexal infections and postoperative wound infections with daily dose of 2 g and was effective in 11 cases out of 12 cases (91.7%), and 81.8% of bacteriological effect was obtained. No side effect was observed. From the above results the usefulness of CMNX in the field of obstetrics and gynecology was suggested.     

Ceftazidime: placental transfer and pharmacokinetic parameters in the third trimester pregnancy

Ceftazidime (CAZ), a newly developed cephalosporin with very high stability to beta-lactamase, was evaluated for its transfer into fetus and amniotic fluid in the third trimester pregnancy, following a single bolus intravenous injection at a dose of 1 g. In subjects with various conditions (background factors) standardized, concentrations of CAZ in maternal venous blood, venous and arterial blood in umbilical cord, and amniotic fluid were determined. High concentration of CAZ (10 micrograms/ml or higher) was found to be maintained in fetal blood and amniotic fluid for ca. 4 hours and ca. 8 hours, respectively, after intravenous injection, showing good placental transfer of CAZ. In view of MICs of CAZ, satisfactory clinical efficacy is expected in perinatal infections.     

Pharmacokinetic, bacteriological and clinical studies of cefuzonam in the field of obstetrics and gynecology

To study the transfer of cefuzonam (CZON, L-105) into female genital organs, concentrations of the compound in pelvic dead space exudate were measured in cases of radical hysterectomy due to cervical cancer and analyzed by the two-compartment model. When CZON 1 g was drip-infused intravenously, the concentration in the cubital vein blood was 46.95 micrograms/ml at 1 hour after the start of infusion. Concentrations in the pelvic dead space exudate reached the peak of 11.29 micrograms/ml at 2.44 hours after the start, were higher than 4 micrograms/ml after 8 hours and were higher than 1.7 micrograms/ml after 12 hours. The area under the concentration-time curve in the pelvic dead space exudate was 77.85 micrograms X hr/ml. From these results CZON was considered to be effective when administered at 1 g against infections of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and haemophilus influenzae, but increased dose levels seemed necessary against infections of Staphylococcus epidermidis and Bacteroides fragilis. In 3 cases of obstetric and gynecological infections the efficacy of CZON was good in 2 cases and unknown in the other case.     

Transplacental transfer and clinical application of aztreonam

Preclinical and clinical studies on aztreonam (AZT) in the perinatal period were carried out and the results are summarized below. 1. Concentrations of AZT in maternal serum, umbilical cord serum and amniotic fluid were measured after intravenous injection of AZT 1 g and 2 g, and intravenous drip infusion of AZT 1 g. As results, the transfer of AZT into umbilical cord serum started to increase in 1 to 2 hours, and the transfer of AZT into amniotic fluid started to increase after an elapse of 2 hours. Upon the intravenous injection of 2 g, AZT concentration in amniotic fluid was as high as 27.1 micrograms/ml even at 10 hours 30 minutes after the injection, and it was still 6.9 micrograms/ml at 20 hours or more after the injection. 2. AZT 2 g/day (b.i.d.) was administered by intravenous drip infusion to 1 perinatal infection case with pyelonephritis. It was clinically effective and neither side effect nor abnormal laboratory test value was observed.     

Basic study on cefminox in the field of obstetrics and gynecology

In patients with carcinoma of the uterine cervix, cefminox (CMNX, MT-141) was given intravenously after panhysterectomy and the pelvic dead space exudate and serum levels of the drug were determined at various periods. The pelvic dead space exudate level reached its peak of 67.21 +/- 39.81 micrograms/ml at 2 hours, which decreased gradually to 26.04 +/- 6.66 micrograms/ml at 6 hours. In the serum, the drug level attained the peak of 152.98 +/- 85.37 of 7.26 +/- 1.66 micrograms/ml was still detected. The pelvic dead space exudate level was much higher than its MIC or 3h-MBC at all periods studied. From these results it was considered that CMNX achieves levels high enough to be expected of clinical efficacy in the pelvic dead space exudate and serum.     

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.     

The clinical usefulness and transference of cefcapene pivoxil (CFPN-PI) into the maternal cubital blood, umbilical blood and amniotic fluid in premature rupture of the membranes

We studied the transference of cefcapene pivoxil (CFPN-PI) into the maternal cubital blood, umbilical blood and amniotic fluid as well as its clinical usefulness. 58 pregnant women without complications who had a premature rupture of membranes after day 0 of the 36th week of pregnancy and delivered a child with a normal transvaginal labor were enrolled this study. As a result, we found that the maternal serum level of CFPN-PI reached a detectable level at 1 hr 15 min post dose, reached the maximum (Cmax) at 2 hr 30 min, and was maintained at 0.15-1.14 micrograms/ml until 4 hr 35 min. In the umbilical serum, the drug concentration reached a detectable level at 1 hr 45 min post dose, was maintained at Cmax of 0.40 microgram/ml from 3 hr 3 min until 4 hr 27 min, and showed a level as high as 0.14 microgram/ml at 7 hr 7 min. In the amniotic fluid, the drug concentration reached a detectable level of 0.09 microgram/ml at 2 hr 48 min post dose, reached Cmax at 3 hr 55 min, and was maintained at 0.15-0.61 microgram/ml until 13 hr 37 min. Concerning the prophylactic effects of CFPN-PI against infections, one case of puerperal intrauterine infection in the parent and two cases of neonatal infection were observed, showing an effectiveness of 95%. In terms of adverse events, neither abnormality in maternal laboratory test data suspected as due to CFPN-PI, nor abnormality in subjective and objective findings was observed. In the neonates, no abnormality suspected as due to CFPN-PI was detected, either, including growth retardation until the 3-month medical examination. We think that CFPN-PI can be a first choice drug for prophylaxis of infections in cases of premature rupture of membranes after the 36th week of pregnancy, because of convenience of oral administration, coupled with excellent safety and potent prophylactic effectiveness against infections resulting from a long term maintenance of high levels in the umbilical blood and amniotic fluid.     

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 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 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.     

A novel pharmacokinetic method for analysis of placental transfer of latamoxef in humans

A novel pharmacokinetic method was developed for analysing the behaviour of a drug in tissues. The absolute transfer ratio of a drug to a tissue was defined using the pharmacokinetic parameters obtained by this method. Composite data of latamoxef (moxalactam) concentration in maternal blood, umbilical cord blood and amniotic fluid following a 2g intravenous injection to pregnant women at delivery were analysed by this method to study the drug behaviour in pregnant women, fetuses and amniotic fluid. Latamoxef kinetics in pregnant women at full term were generally similar to that in previously reported healthy subjects. The concentration of latamoxef in umbilical cord blood peaked about 2 hours after dosing then decreased in parallel with the maternal blood concentration. The amniotic fluid concentration peaked about 7 hours after administration, then decreased slowly. The absolute transfer ratios to fetus and amniotic fluid were calculated to be about 2.5 and 0.37% respectively.     

Placental transfer and hormonal effects of metoclopramide

In order to study the transplacental transfer of metoclopramide, and its endocrine effects, measurements were made of its concentration in maternal and fetal blood, and in the amniotic fluid, together with maternal and fetal plasma concentrations of prolactin, TSH and oestradiol, during delivery by selective Caesarean section. The drug, 10 mg, was injected i.m. 12 and 2 h and just before the onset of anaesthesia. Metoclopramide was detectable in all the umbilical arterial and venous and amniotic fluid samples, in mean concentrations of 50, 63 and 75 ng/ml, respectively. The mean ratio between the umbilical venous and maternal plasma concentrations was 0.63. Accurate maternal plasma half-lives could not be established but they must have averaged 2 to 4 h. The high amniotic fluid concentrations and relatively high umbilical venous and arterial concentrations soon after administration suggest that metoclopramide equilibrates relatively rapidly between the mother and fetus. Metoclopramide raised the maternal plasma prolactin levels from 315 +/- 128 ng/ml (SD) before therapy to 357 +/- 112 ng/ml at the time birth. No statistically significant difference in cord arterial or venous plasma prolactin levels was seen between the control and metoclopramide-treated groups. Metoclopramide did not affect maternal plasma TSH or oestradiol levels. The only change was a slight but significant increase in TSH level in cord blood taken from the umbilical artery after metoclopramide treatment.     

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.     

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)