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 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.     

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.     

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.     

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.     

Basic and clinical studies on ceftazidime in the field of obstetrics and gynecology

Ceftazidime (CAZ), a new cephalosporin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of CAZ into intrapelvic genital organs were good after a single drip infusion of 1.0 g for 30--60 minutes. The maximum level of 76.4 micrograms/ml was obtained in uterine artery serum at 8 minutes after administration. The high concentrations were also obtained in genital tissues; the maximum concentrations ranged from 46.8--62.1 micrograms/g at 20 minutes after administration and the levels were as high as 2.1--7.7 micrograms/g at 5 hours and 40 minutes after administration. The concentration curves in tissues were consistent with those of serum levels. The concentrations of CAZ in retroperitoneal dead space exudate were determined after intravenous drip infusion of 1 g. The peak levels ranged from 26 to 32 micrograms/ml after 30 minutes of administration and the level of 8.53 micrograms/ml was sustained even 6 hours later. Good response was obtained in cases of gyneco-obstetric infections such as intrauterine infection, intrapelvic infection and external genital infection with daily dose of 2--4 g. CAZ was effective in 13 out of 14 cases (the efficacy ratio; 92.9%). As to side effects, gastric discomfort and vomiting were observed in 1 case.     

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

Pharmacokinetic and clinical studies on cefuzonam (CZON) were performed to evaluate its usefulness in the field of obstetrics and gynecology. A summary of the results is as follows: 1. Concentrations of CZON in female genital organ tissues showed a little variance among organs. Mean concentrations were 3.34-7.83 micrograms/g at 40 minutes, 0.523-1.08 micrograms/g at 2 hours 15 minutes and 0.286 micrograms/g (in the myometrium) at 3 hours 10 minutes after the end of drip infusion. 2. Mean concentrations of CZON in the pelvic dead space exudate were 31.0 micrograms/ml immediately after the end of drip infusion (1 hour after the start of infusion), and 37.2 micrograms/ml 1 hour after the end of infusion, then they gradually decreased to 25.6 micrograms/ml after 3 hours and 21.4 micrograms/ml after 5 hours. Mean serum concentrations of CZON in concurrently collected samples from the peripheral vein were 30.0 micrograms/ml immediately after the end of drip infusion, 14.4 micrograms/ml after 1 hour, 4.00 micrograms/ml after 3 hours and 1.84 micrograms/ml after 5 hours. The T 1/2 beta was 1.03 hours. 3. Clinical trial in 7 patients, with CZON administered at a dose level of 1 g at a time, twice daily, showed "excellent" and "good" efficacy in all the patients. No side effects were noted. From the results of the above studies, CZON seems to be highly useful for infections in the field of obstetrics and gynecology.     

Experimental and clinical evaluation on ceftriaxone in the field of obstetrics and gynecology

Ceftriaxone (CTRX), a new cephalosporin antibiotic, was evaluated in the field of obstetrics and gynecology and the following results were obtained. The concentration of CTRX after an intravenous injection with 1 g was determined in the uterine artery, cubital vein and in the intrapelvic genital tissues such as the oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis. The peak level was 160 micrograms/ml at 26 minutes after injection both in the uterine arterial serum and cubital venous serum, 48 and 38 micrograms/g at 1 hour and 18 minutes in the tissues of oviduct and ovary, respectively, 54 and 50 micrograms/g at 48 minutes in the myometrium and cervix uteri, respectively, while 46 micrograms/g at 39 minutes in the portio vaginalis. The mean level 18 to 24 hours after administration was 19 micrograms/ml in the uterine arterial serum and cubital venous serum and 6.3 micrograms/g in the intrapelvic genital tissues. A case of intrapelvic infection clinically showed an excellent response without any side effects by intravenous drip infusion with 2 g divided as twice a day for 7 days. The above results show that CTRX is useful in the field of obstetrics. and gynecology.     

Fundamental and clinical evaluation of cefodizime in obstetrics and gynecology

Cefodizime (CDZM, THR-221), a newly developed injectable cephem antibiotic agent, was evaluated for its distribution in intrapelvic genital organ tissues, penetration into exudate of retroperitoneal space and breast milk and therapeutical effects on some infections in obstetrics and gynecology. The results obtained are summarized as follows. 1. When 1 g of CDZM was administered by drip infusion over a 60 minutes period, its serum concentration reached 53.51 micrograms/ml at the completion of drip infusion, then declined rapidly. Peak concentrations of CDZM in intrapelvic genital organ tissues were higher than 20 micrograms/g at different times. CDZM was transferred to the exudate of retroperitoneal space and its concentration reached a peak of 7.01 micrograms/ml at 2.67 hours after initiation of 60 minutes drip infusion at a dose of 1 g, then declined slowly but stood at 4.93 micrograms/ml even at 8 hours. The transfer of CDZM to breast milk was similar to other cephem antibiotic agents and peak levels of CDZM in milk were 0.13-0.36 microgram/ml at 2 or 3 hours after administration of a dose of 1 g. 2. In the clinical study, CDZM was administered by drip infusion over 60 minutes to 6 patients with obstetrical and gynecological infections at a daily dose of 2-6 g. Clinical results were good in 5, poor in 1, and the efficacy rate was 83.3%. No side effects nor abnormal laboratory test results were observed.     

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.     

In vitro activity and clinical evaluation of aztreonam in the field of obstetrics and gynecology

Antimicrobial activity of aztreonam (AZT) against 231 clinical isolates in the field of obstetrics and gynecology was determined by agar-plates dilution method. Almost of all strains of E. coli (108 strains) tested were susceptible to the concentration of 0.20 micrograms/ml of AZT. Anaerobic bacteria, however, were less susceptible to this antibiotic than to cefazolin. The concentrations of AZT were determined in serum and pelvic tissue samples obtained at various intervals after 1 hour intravenous drip infusion with 1 g. The concentrations of AZT in pelvic tissues were maximal 9.3 micrograms/g at 57 minutes but less than 0.6 micrograms/g at 3 hours or more after injection. Clinical efficacy of AZT was evaluated in 6 cases consisted of two each with Bartholin's abscess and intrauterine infection and one each with post partum endometritis and acute adnexitis. Clinical efficacies were seen in 5 cases.     

Basic and clinical studies of aztreonam in the field of obstetrics and gynecology

Aztreonam (AZT), a new monobactam antibiotic, was basically and clinically applied to the field of obstetrics and gynecology, obtaining the following results. The pelvic dead space exudate level of AZT after 30 minutes-intravenous drip infusion of 1 g attained the peak of 22.66 micrograms/ml at 1 hour from initiation of infusion and thereafter declined gradually, contrasting the peak of 34.38 micrograms/ml of the cubital vein at 30 minutes. Total of 13 cases comprising 4 with intrauterine infection, 5 with adnexitis and 4 with pelveoperitonitis were intravenously treated with AZT at a dose of 1 g twice daily. The overall clinical results were excellent in 3 cases and good in 10 cases. No side effects were observed in any of the cases treated with AZT.     

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)     

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

Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and tissue penetration of AC-1370 into intrapelvic genital organs were good. The peak serum level in the uterine artery after an intravenous drip infusion for 30 minutes was 49.0 micrograms/ml. High concentrations were obtained also in genital organ tissues; the maximum concentrations were 24.4 approximately 39.0 micrograms/g after an intravenous drip infusion. The changing patterns of the tissue concentrations were similar to those in the serum. The penetration of AC-1370 into intrapelvic dead space exudate was good. The level reached a peak of 35 micrograms/ml at 2 approximately 4 hours after an intravenous drip infusion with 1 g and 3.7 micrograms/ml after 12 hours. AC-1370 was effective in 20 out of 21 cases (95.2%) with gynecoobstetrical infections such as intrauterine, intrapelvic infection and mammitis, administered with 1 approximately 2 g twice a day. Few side effects were observed.     

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.     

Pharmacokinetics and clinical studies of aztreonam in neonates and premature infants

Pharmacokinetics and clinical evaluation of aztreonam (AZT) in the neonates and premature infants were studied with the following results: 1. Serum concentrations of AZT in 60 minutes intravenous drip infusion of AZT 20 mg/kg to 6 cases of neonates with 2 to 22 days of age were 45.5 +/- 0.87 micrograms/ml immediately after the completion of intravenous drip infusion, 37.8 +/- 1.62 micrograms/ml 1 hour after, 31.2 +/- 1.92 micrograms/ml 2 hours after and 19.7 +/- 2.36 micrograms/ml 4 hours after, respectively. Serum half-life was 3.61 +/- 0.53 hours on the average. 2. Urinary excretion rate 6 hours after intravenous drip infusion was 26.4 +/- 6.86% on the average. 3. Clinical evaluation was given to 1 sepsis case of 7-days of age and it was effective. There was no abnormal clinical or laboratory finding considered to be associated with AZT.     

Laboratory and clinical studies of T-1982 (cefbuperazone in pediatric field

The authors have carried out the laboratory and clinical studies of T-1982 (cefbuperazone). The results were as follows: The sensitivity was estimated by the plate dilution method on 28 strains of S. aureus 26 strains of E. coli, 27 strains of K. pneumoniae, 25 strains of S. marcescens and 14 strains of Proteus sp. isolated from patients. The distribution of susceptibility of S. aureus was 1.25-25 micrograms/ml and the peak of distribution was 12.5 micrograms/ml. The strains of 84.6% of E. coli were inhibited at concentration of less than 0.39 micrograms/ml. The strains of 77.8% of K. pneumoniae were inhibited at concentration of less than 0.2 microgram/ml. The strains of 96% of S. marcescens was inhibited at concentration of less than 3.13 micrograms/ml. The distribution of susceptibility of Proteus sp. was 0.39-25 micrograms/ml. T-1982 was given to intravenous administration for 5 minutes and drip infusion for 30 minutes a single dose of 20 mg/kg of T-1982 to 2 and 2 children respectively. After intravenous administration of T-1982, the mean serum level was peak 88.4 +/- 8.7 micrograms/ml at 15 minutes, 52.5 +/- 2.7 micrograms/ml at 1 hour, 4.6 +/- 0.15 micrograms/ml at 6 hours respectively. Half-life was 89 minutes. And after drip infusion of T-1982, the mean serum level was 75.5 +/- 3.5 micrograms/ml at 30 minutes and 3.1 +/- 0.6 micrograms/ml at 6.5 hours respectively. Half-life was 82 minutes. The mean urinary excretion rate was 94.7%, 57.4 +/- 11.0% up to 6 hours after intravenous administration and drip infusion respectively. T-1982 was effective in 13 cases out of 13 cases with bacterial infections. No side effects were observed except for 1 case with elevation of serum GOT, 1 case with elevation of serum GPT and 2 cases with eosinophilia.     

Clinical study on transfer into lung tissue and postoperative prophylactic effect of new cephamycin antibiotics, particularly cefotetan and cefbuperazone

The following findings were obtained in our clinical study on the transfer of cefotetan (CTT) and cefbuperazone (CBPZ), new antibiotics of cephamycin series, into the lung tissue and on their postoperative prophylactic effect. 1. The mean serum concentration 30 minutes after the start of an intravenous drip infusion of 1 g of CTT over a period of 30 minutes was 99.4 micrograms/ml, and it decreased gradually thereafter with the half-life of 2.45 hours. After an intravenous drip infusion of 1 g of CTT over a period of 1 hour, the mean peak concentration of 104.1 micrograms/ml appeared 1 hour after the start of the infusion, and mean concentrations at 2, 4 and 6 hours after the infusion were 63.4, 34.3 and 27.0 micrograms/ml, respectively, with the half-life of 2.35 hours during phase beta. 2. Following 30 minutes of an intravenous drip infusion of CTT, the tissue CTT level in normal lung tissues was Tmax 1.82 hours and Cmax 19.8 micrograms/g. After 1 hour of an intravenous drip infusion the mean concentration in the tissues was at the peak of 39.7 micrograms/g in 2 hours after the start of an administration, while mean levels at 3, 4 and 6 hours after an administration were 32.2, 22.2 and 8.76 micrograms/g, respectively, with Tmax of 1.82 hours and Cmax of 30.5 micrograms/g. 3. Following an intravenous drip infusion of 1 g of CBPZ over a period of 1 hour, the mean serum drug concentration 1 hour after the start of infusion was at its peak, 83.3 micrograms/ml, while mean values at 2, 4 and 6 hours after the start of an administration were, respectively, 40.4, 19.8 and 9.62 micrograms/ml, with the beta-phase half-life of 2.03 hours. 4. By 1 hour after the start of intravenous drip infusion of CBPZ, the mean tissue level in normal lung tissues was at the peak of 31.6 micrograms/g, while mean levels at 3, 4 and 8 hours after an administration were 16.2, 11.0 and 4.56 micrograms/g, respectively, with Tmax of 1.67 hours and Cmax of 21.9 micrograms/g. 5. Infused CBPZ was transferred into bronchiole tissues. Drug concentrations in these tissues at 3 and 5 hours after the start of the infusion were 7.87 and 4.85 micrograms/g, respectively, with their ratios to the peak serum level were 9.4 and 5.8%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

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 aztreonam

Aztreonam (AZT), a new monocyclic beta-lactam antibiotic, was studied on the transfer into intrapelvic tissues and on the clinical efficacy in the treatment of 19 cases of obstetrical and gynecological infections. The AZT levels were examined in the pelvic dead space exudate in 6 patients who received radical hysterectomy due to uterocervical cancer. The simulation curves for AZT were well performed after the decision of the pharmacokinetic parameters using the two-compartment model. Following 1-hour intravenous drip infusion of 1 g of AZT, the peak concentration of AZT in cubital venous blood was estimated 73.3 micrograms/ml at the end of infusion. The peak concentration of AZT in the pelvic dead exudate was estimated 18.6 micrograms/ml at 2.31 hours after infusion. Following intravenous 1-hour drip infusion of 1 g, the transferred level of AZT into uterine tissues was maintained at the effective concentration which means the excess level of the MIC against clinical isolates often observed in the field of obstetrics and gynecology. AZT was administered 2-4 g/day in 2 times a day by intravenous drip infusion for 60-90 minutes. The subjects were 19 patients with the following infections; pyometra (1), puerperal intrauterine infection (4), postoperative parametritis (4), pelvioperitonitis (2), purulent lymphocyst (1), acute salpingoophoritis (1), vaginal stump abscess (1), Douglas abscess (2), pelvioperitonitis + pyosalpinx (2), vulval abscess (1). Clinical efficacy was; excellent in 2 cases, good in 11 cases and poor in 6 cases. No notable side effect or abnormal laboratory finding was noted.