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)     

Studies on flomoxef in the perinatal period

Pharmacokinetic, bacteriological and clinical studies on flomoxef (FMOX) in the perinatal period were carried out with the following summary of the results. Antibacterial effects of FMOX on the growth of methicillin-resistant Staphylococcus aureus (MRSA, MIC 400 micrograms/ml), methicillin-sensitive S. aureus (MSSA, MIC 0.78 microgram/ml), Escherichia coli (MIC 3.13 micrograms/ml and MIC 0.20 microgram/ml) in amniotic fluid were determined and it was found that the activity of FMOX was enhanced in the amniotic fluid. FMOX rapidly penetrated into tissues and sera of pregnant women upon intravenous injection and its maternal serum concentrations reached their peak levels shortly after administration. Placental penetration of FMOX to the fetus was good and, after single intravenous injection of 1 g, the concentrations of FMOX in the umbilical cord serum and amniotic fluid exceeded MICs against major causative organisms of perinatal infections. These results indicate that single intravenous injection of FMOX 1 g twice a day is effective for the treatment and prophylaxis of perinatal infections. Injection of FMOX for the treatment of 14 cases of puerperal infections showed excellent clinical effectiveness with 100% clinical effect and 81.8% bacteriological response. No side-effect was observed in any case. All of these results suggested clinical usefulness of FMOX in the perinatal period.     

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.     

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.     

Studies on imipenem/cilastatin sodium in the perinatal period

Pharmacokinetic, bacteriological and clinical studies of imipenem/cilastatin sodium (IPM/CS) were carried out in the perinatal period, and the results obtained are summarized as follows: Effects of IPM on bacterial growth curves of Staphylococcus aureus (sensitive and resistant strains) and Escherichia coli (sensitive strains) in amniotic fluid were determined. The bactericidal effects of IPM increased in amniotic fluid and remarkable increases against resistant strains were demonstrated. IPM and CS were detected promptly after intravenous drip infusion to pregnant women, and reached peak levels shortly after administration in maternal plasma. Placental penetration of IPM and CS to the fetus was favorable. After intravenous drip infusion of 500 mg/500 mg of IPM/CS, drug concentrations in the umbilical cord plasma and the amniotic fluid exceeded MICs against main pathogenic organisms. Clinically, IPM/CS was effective in the treatment of perinatal infections without any side effect. The above results demonstrated that IPM/CS is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.     

头孢唑肟酸合成方法研究

目的 优化头孢唑肟酸合成条件.方法 考察四氢呋喃,乙酸乙酯,二氯甲烷,N,N-二甲基乙酰胺四种溶剂对7-氨基-3-去甲基-3-头孢烷酸(7-ANCA)与2-(2-氨基4-噻唑基-2-甲氧亚胺乙酸苯并噻唑硫酯(AE活性酯)合成头孢唑肟酸收率的影响.结果 确立了较优合成工艺条件:以乙酸乙酯为溶剂,n(7.ANCA):n(AE活酯):n(三乙胺)=1:1.2:2时,产品收率91.8%,纯度99.85%(HPLC),产品质量符合药典标准.结论 此方法简捷、易于产业化.     

Study on cefotiam in the perinatal period

Cefotiam (CTM), a new cephem antibiotic with high activity against Gram-positive and Gram-negative bacteria, has been investigated for use in 60 mothers in perinatal period, and following results were obtained. The concentration of CTM in maternal serum was 38 micrograms/ml at 0.5 hour after an intravenous administration of 1 g. A good transport of CTM into umbilical cord serum and amniotic fluid was observed after the intravenous administration into the mother. No adverse effect appeared in the neonates. The CTM is highly useful antibiotic in perinatal infections, and the safe dose of CTM to the mother in perinatal period is considered to be 1-2 g per day.     

Study on flomoxef in the perinatal period

The placental passage and the the therapeutic efficacy of flomoxef (FMOX, 6315-S) were studied in patients in the perinatal period. A summary of the obtained results is as follows: 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid obtained upon one-shot intravenous injections to 12 patients were compared with those obtained upon 1 hour drip infusions to 9 patients. It was found that the former means of administration gave higher concentrations that the latter. 2. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid at 1 to 6 hours after administration through either method were all higher than MIC80's of recognized bacteria. 3. Clinical efficacies were evaluated in 10 patients with puerperal intrauterine infection, 7 patients with endometritis, 2 patients with pyelonephritis and 1 patient each with endo-cervicitis, amniotic fluid infection, mastitis and perineal wound infection. Clinical efficacies were excellent in 5 patients (21.7%), good in 17 patients (73.9%) and poor in 1 patient (4.4%), thus the overall efficacy rate was 95.7%. 4. Eradication of causative bacteria were obtained in all 8 cases tested, hence the eradication rate was 100%. 5. Mild diarrhea in 1 patient was the only side effect observed. No abnormal clinical laboratory test results were found in any patients.     

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.     

Clinical evaluation of latamoxef in the perinatal period

Latamoxef (LMOX), a new oxacephem antibiotic with high activity against Gram-negative bacteria has been investigated for use in No. of 58 mothers in perinatal period, and obtained following results. Concentration of LMOX in maternal serum was 43.4 micrograms/ml at the 1 hour after intravenous administration of 1 g. In umbilical cord serum and amniotic fluid, LMOX showed good translation after intravenous administration of 1 g into the mother, but no adverse effect appeared in the neonate. LMOX is highly useful antibiotic in perinatal infections, and the safe dose of LMOX to the mother in perinatal period is 1--2 g per day considerably.     

A study on ceftriaxone in the perinatal period

Ceftriaxone (CTRX), a new cephem antibiotic with high activity against Gram-positive and Gram-negative bacteria, was investigated pharmacokinetically in 30 mothers in the perinatal period. The obtained results are summarized below. 1. The maximum CTRX level in the maternal serum was 135 micrograms/ml between 20 and 25 minutes after an intravenous administration of 1 g of CTRX. 2. The transfer of CTRX into the umbilical cord serum and the amniotic fluid was very good. CTRX levels in these fluids were about 20% and 10% of the maternal serum level, respectively. 3. No side effect was observed in mothers or neonates. 4. CTRX is a useful antibiotic for perinatal infections.     

A study on ceftazidime in the perinatal period

Ceftazidime (CAZ), a new cephem antibiotic with high activity against Gram-negative bacteria, has been investigated for use in mothers in perinatal period, and the results obtained are summarized below. Into maternal serum, umbilical cord serum and amniotic fluid, CAZ showed good transfer after intravenous administration of 1 g or 2 g into mothers, and no adverse effect appeared in their neonates. The CAZ is a very useful antibiotic for the prophylaxis and the treatment of perinatal infections at a dose level of 1-2 g per day.     

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.     

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.     

Effects of dietary phytoestrogen exposure during perinatal period

Developmental effects of phytoestrogens were studied in offspring from pregnant rats who received a free-feeding diet of either rat chow that was very low in phytoestrogens (low phyto), rat chow low in phytoestrogens and given a genistein and diadzein supplement tablet (high phyto), or normal rat chow (normal) from the second week of pregnancy to weaning (postnatal day 21). Measurements of anogenital distance, daily weights, righting reflex and ultrasonic vocalizations were made on neonatal pups and plasma testosterone and corticosterone were assessed in adult males. There was a significant effect of phytoestrogen treatment on USV for all male and female offspring. Differences between groups in daily weights and anogenital distance were attributed to the micronutrient levels of the two rat chow types employed in this study. No differences in righting reflex test, corticosterone levels or testosterone levels were found among treatment conditions. These results are the first demonstration of phytoestrogens affecting USVs and underscore the complexity of the effects of these substances on biobehavioral development.     

Fundamental and clinical studies on cefmenoxime in perinatal period

Pharmacokinetic studies and clinical evaluations of cefmenoxime (CMX) were carried out in perinatal mothers and infants. The following results obtained are summarized as follows. 1. CMX was promptly absorbed upon intravenous injection in pregnant women, reached dose-related peak serum level shortly after administration. Placental penetration into the fetus occurred quickly and at high levels. After intravenous injection of 1 g of CMX, drug concentrations in the cord blood and amniotic fluid exceeded MICs of main pathogenic organisms. The drug transferred into newborn infants were followed by measuring serum level of the newborn. These levels were related to levels of umbilical cord blood and the drug was eliminated gradually from the newborn without accumulation. According to the above results, it appears possible to successfully prevent or treat perinatal infections, through administration of the dose of 1 g twice daily. 2. Clinically, CMX was effective in the treatment of perinatal infections and prophylaxis of intra-uterine amniotic infections without any severe side effect. 3. Moreover, newborn infants delivered from mothers receiving CMX treatment were without abnormalities in laboratory test results. 4. The penetration of CMX into mother's milk was hardly observed and the transference from milk to newborn infants appeared to be occur only at very low levels. The above results have demonstrated that CMX is a clinically useful antibiotic for prophylaxis and treatment of perinatal infections.