Pharmacokinetic and clinical studies on cefodizime in the field of obstetrics and gynecology

Pharmacokinetic and clinical studies on cefodizime (THR-221, CDZM) were carried out and the following results were obtained. Concentrations of CDZM in serum and uterine tissues were determined from 38 to 282 minutes after drip infusion of 1 g CDZM. CDZM reached peak level of 25.0 micrograms/g or higher in each tissue during a period of 38 to 83 minutes. Concentrations of CDZM in the dead space exudate after drip infusion of 2 g CDZM were also studied. At 240 minutes after injection, CDZM concentration in exudate reached a peak of 46.88 micrograms/ml. These levels far exceeded MICs of CDZM against major pathogens most often isolated in the field of obstetrics and gynecology. CDZM was administered to 7 patients with their diseases diagnosed as pelvic peritonitis (4 cases) or acute adnexitis (3 cases) at a dose of 2-4 g per day for 6-14. days. Clinical response was good in all cases. Transient elevation of liver function was noticed in 2 cases. No other adverse reactions were noted during the study.     

Pharmacokinetic and clinical studies on cefodizime in obstetrics and gynecology

Cefodizime (CDZM), a new cephem antibiotic, was studied in terms of its pharmacokinetics and clinical efficacy in the field of obstetrics and gynecology, and the results are summarized as follows: Concentrations of CDZM in serum and genital tissues following 1 g drip infusion (30 min.) were determined and good penetration of CDZM into tissues was recognized. The maximum level in uterine arterial serum was 56.25 micrograms/ml and maximum tissue levels ranged 23.56-40.64 micrograms/g which were above its MIC80's for main pathogenic organisms. Peak concentrations of CDZM in pelvic dead space exudates following 1 g intravenous bolus injection or drip infusion ranged 6.25-6.52 micrograms/ml. The clinical efficacy of CDZM in 17 cases of obstetrical and gynecological infections was investigated using a dose of 1-3 g daily. The clinical efficacy rate was 88.2% (15/17 cases). Bacteriologically, the eradication rate was 83.3%. No side effects or abnormal laboratory test values were observed.     

Clinical studies on cefodizime in the field of obstetrics and gynecology

Clinical studies on cefodizime (THR-221, CDZM), a new injectable cephem antibiotic, were performed and the following results were obtained. Ten patients with obstetrical and gynecological infections such as intrauterine infections, pyometra, adnexitis, parametritis and lymphocystitis. The clinical results were evaluated as excellent in 1 case, good in 4 cases and poor in 5 cases. The efficacy rate was 50.0%. Bacteriologically, 10 organisms were isolated from 8 patients and the eradication rate was 44.4%. No side effects were observed in any of the cases treated with CDZM. In laboratory examinations, transient elevations of serum GOT, GPT and Al-P were noted 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.     

Pharmacokinetic and clinical studies on latamoxef in the field of obstetrics and gynecology

Latamoxef (LMOX) 1 g was administered twice daily for 5 days to patients undergoing operation for myoma uteri and the time course of tissue concentrations of the drug and the prophylactic effect of the treatment on postoperative infection were studied. 1. Area under concentration-time curve (AUC) of LMOX was the highest in the perimetrium (45.3%), followed by the cervix uteri (39.2%), endometrium (35.9%), oviduct (35.1%), myometrium (29.5%), and ovary (24.4%). 2. Cmax was the highest in oviduct (46.9 micrograms/g), followed by Cmax's in perimetrium (44.2 micrograms/g), cervix uteri (35.8 micrograms/g), myometrium (26.9 micrograms/g), endometrium (25.6 micrograms/g), and ovary (24.3 micrograms/g). 3. Serum half-lives were T1/2(alpha) = 0.27 hour and T1/2(beta) = 1.81 hours. 4. Prophylactic efficacy against postoperative infections was 94.3%, and febrile morbidity was 5.7%. The preoperative and postoperative laboratory tests did not show appreciable changes, no adverse reaction was observed. In the present study, LMOX showed good transfer into gynecological tissues, suggesting its very high usefulness in the treatment of infection and in the postoperative management.     

Pharmacokinetic and clinical studies on ceftriaxone in the field of obstetrics and gynecology

Ceftriaxone (CTRX) was studied regarding its penetration into the adnexa uteri and uterine tissues, as well as its utility and safety in the treatment of patients with obstetric and gynecologic infections. The results obtained are summarized below. 1. When 1 g of CTRX was administered by intravenous bolus injection, Cmax in tissues of adnexa uteri and uterus ranged from 42.2 to 80.5 micrograms/g, Tmax ranged from 0.42 to 0.81 hour, and the AUC ranged from 314.9 to 606.9 micrograms.hr/g. Thus, drug penetration into these tissues was good. 2. Clinical efficacy of CTRX was evaluated in 29 obstetric and gynecological patients. The clinical efficacy was good in all cases. 3. Bacteriological effects of CTRX were very good, and 90% of the organisms isolated before treatment were eradicated. 4. Laboratory testing revealed an occurrence of mild eosinophilia in 1 case.     

Pharmacokinetic and clinical study on cefodizime in obstetrics and gynecological field

Clinical investigation of cefodizime (CDZM, THR-221), a newly developed cephem antibiotic, was carried out with regard to its distributions to genital organs, and the drug was evaluated clinically against infections in obstetric and gynecological fields. 1. Distributions to genital organs One gram of CDZM was administered to each patient who received simple total hysterectomy by 1 hour intravenous drip infusion and concentrations of CDZM in genital organs such as antecubital vein, uterine artery, ovary, oviduct, endometrium, myometrium, cervix uteri and portio vaginalis were examined. Serum concentrations were elevated to an average of 90.63 micrograms/ml in 15 minutes after administrations of CDZM and decreased gradually at fixed times. CDZM was distributed in concentration ranges of 45.32-10.96 micrograms/g in ovary, 26.58-10.20 micrograms/g in oviduct, 42.20-9.80 micrograms/g in endometrium, 31.28-11.72 micrograms/g in myometrium, 42.20-12.52 micrograms/g in cervix uteri and 45.32-9.40 micrograms/g in portio vaginalis, and these high concentrations lasted more than 3 hours after administrations. 2. Clinical evaluations CDZM was given to 10 patients, including 7 cases with pelvioperitonitis and 1 case each with pyometra, Bartholin's abscess and puerperal fever, at a dose level of 1 or 2 gram 2 times daily by 30-60 minutes intravenous drip infusion. Overall clinical efficacies were excellent in 3 cases and good in 7 and the efficacy rate was very high, at 100%. Bacteriological efficacies were eradicated in 6 cases, and unknown in 2, and the eradication rate was 100%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic and clinical studies on cefodizime in gynecologic field

Pharmacokinetic and clinical studies on a new cephalosporin antibiotic, cefodizime (THR-221, CDZM), were performed and the results obtained are summarized as follows: 1. At about 84 minutes after a bolus injection of 1 g dose of CDZM, the drug was transferred well into tissues of internal genital organs and remained there at therapeutic levels for 285 minutes. The drug was also transferred quickly and sufficiently into exudate from pelvic dead space and its levels were still kept at high levels at 6 hours after administration. 2. CDZM was given to 8 women affected with gynecologic infections. The outcome of CDZM therapies showed that the drug was effective in all 8 of patients (100%) clinically and bacteriologically. 3. Notable adverse effects or abnormal laboratory test results were not observed except for 2 patients with transient and slight elevation of transaminase levels. Based on these results, it may be concluded that CDZM is a highly effective and a very safe antibiotic for the treatment on infectious diseases in gynecologic field.     

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.     

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

Cefuzonam (CZON, L-105), an antibiotic injectable of cephalosporin family, was studied pharmacokinetically, clinically and bacteriologically to examine its distribution to female genital tissues and the activity on infections in the field of obstetrics and gynecology. Maximum concentrations in serum and genital tissues achieved 19-46 minutes after intravenous injection of CZON 1 g were 69.6 micrograms/ml for serum, 63.1 micrograms/g for oviduct, 34.2 micrograms/g for ovary, 22.5 micrograms/g for endometrium, 33.4 micrograms/g for myometrium, 30.7 micrograms/g for cervix uteri, and 37.1 micrograms/g for portio vaginalis. Clinical efficacies on 15 cases of intrauterine infection and adnexitis were proved with 4 cases of 'marked improvement' and 11 cases of 'improvement', thus the efficacy rate was 100%. Of 21 strains of aerobes and anaerobes isolated from infectious lesions, 19 strains were eliminated after administration of the drug. No side effects were observed. From these results of fundamental and clinical studies CZON appeared to be a highly useful drug fro the obstetric and gynecological infections.     

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

The distribution of cefuzonam (CZON, L-105) into the uterus and uterine adnexa was investigated and the usefulness and the safety of CZON in obstetric and gynecological infections were studied. The results are summarized as follows: 1. Following one shot intravenous injection of CZON 1 g, a good distribution of the drug into tissues of uterus and uterine adnexa was observed, with Cmax values of 15.7-33.9 micrograms/g, Tmax of 7.3-34.0 minutes and AUC values of 18.7-35.3 micrograms X hr/g. 2. In all of the 30 cases of obstetric and gynecological infections treated, CZON was evaluated effective. 3. Bacteriologically, 93.9% of total bacteria that had been isolated were eliminated by the administration of the drug. 4. Against all the strains of bacteria isolated before the treatment and replaced bacteria, MIC50, MIC80 and MIC90 of CZON were 0.20 micrograms/ml, 12.5 micrograms/ml and 25 micrograms/ml, respectively, showing low values. 5. Subjective and objective findings and clinical laboratory test values during and after the trial showed no side effects associated with CZON.     

Pharmacokinetic and clinical studies on cefuzonam in obstetrics and gynecology

Cefuzonam (CZON), a new cephem antibiotic agent, was studied in terms of its pharmacokinetics and clinical efficacy in the field of obstetrics and gynecology, and the results were summarized as follows. 1. The absorption and the tissue penetration of CZON into intrapelvic genital organs were good. The peak serum level in uterine artery after an intravenous drip infusion of 1.0 g was 49.0 micrograms/ml, and the highest peak level of 23.0 micrograms/g in tissues was obtained. After drip infusion of 2.0 g, the peak serum level in uterine artery was 137 micrograms/ml and the highest peak tissue concentration was 54.6 micrograms/g. Tissue concentrations of the drug changed in a similar pattern to serum levels and a dose-dependent response was recognized. 2. The penetration of CZON into intrapelvic dead space exudate was good. The level reached a peak of 8.17 micrograms/ml 4 hours after and intravenous drip infusion of 1.0 g and diminished slowly. 3. The clinical efficacy of CZON at a daily dose of 2 g was evaluated in 21 cases of obstetrics and gynecologic infections. The efficacy rate was 85.7% (18/21 cases). Bacteriologically, the eradication rate obtained was 93.3%. No side effects or abnormal laboratory values were observed.     

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology

Imipenem/cilastatin sodium (MK-0787/MK-0791) was studied for its penetration into the adnexa uteri and uterine tissue, as well as for its clinical efficacy in the treatment of patients with obstetric and gynecologic infections. The following results were obtained. When 500 mg/500 mg of MK-0787/MK-0791 was administered by an intravenous drip infusion, peak levels of MK-0787 in tissues of adnexa uteri and uterus ranged from 14.6 micrograms/g to 25.8 micrograms/g, Tmax ranged from 0.55 hour to 0.98 hour, and the AUC ranged from 25.6 micrograms X hr/g to 45.2 micrograms X hr/g. Thus, the penetration of the drug into these tissues was good. Clinical efficacy of MK-0787 was evaluated in 30 patients in the field of obstetrics and gynecology. The clinical efficacy was excellent or good in all patients. Bacteriological effects of MK-0787/MK-0791 were very good, and 90% of the organisms detected before the treatment were eradicated. The antimicrobial activity of MK-0787 was tested against pathogens isolated before, during and after the treatment. Mean MIC80 values of MK-0787 were 0.39-0.78 micrograms/ml against all Gram-positive bacteria, 0.20-0.39 micrograms/ml against all Gram-negative bacteria, and less than or equal to 0.10-0.20 micrograms/ml against all anaerobic bacteria. The antimicrobial activity of MK-0787 appeared very good. No side effects or abnormal laboratory findings were observed except a slight elevation of S-GPT in 1 patient.     

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 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, bacteriological and clinical studies of cefuzonam in the field of obstetrics and gynecology. Study group of cefuzonam in the field of obstetrics and gynecological infections

A multi-center open study was conducted to investigate cefuzonam (CZON, L-105) regarding to its pharmacokinetic, bacteriological and clinical aspects in the field of obstetrics and gynecology with the participation of 31 medical institutions and the related facilities. The results are summarized as follows. 1. Peak MICs of CZON for Staphylococcus aureus, coagulase (-) staphylococci, Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis group, Peptostreptococcus spp. isolated from obstetrical and gynecological infections with relatively high frequencies were 0.39, 0.20, 0.024, 0.024-0.05, 12.5, 0.20 microgram/ml, respectively, with an inoculum size of 10(6) CFU/ml. 2. When 1 g of CZON was given through bolus injection, the maximum concentration (Cmax) of CZON in pelvic dead space exudate was 18.7 micrograms/ml at 60.9 minutes (Tmax) after the injection; Cmax's in all female genital tissues were observed at 0.6-27.9 minutes and ranged from 11.9-26.3 micrograms/g. The Cmax 8.3 micrograms/ml, in the pelvic dead space exudate was noted at 97.0 minutes after the end of the intravenous drip infusion of 1 g over 1 hour, and Cmax's in genital tissues were 14.3-30.0 micrograms/g at the end of infusion. With 1 hour drip infusion of 2 g, Cmax's in genital tissues were 35.0-53.9 micrograms/g at the end of infusion. 3. The clinical efficacy of CZON was evaluated in 206 evaluable patients with obstetric and gynecologic infections. Efficacy rates classified by types of infections were 97.1% (67/69) for intrauterine infections, 81.6% (31/38) for intrapelvic infections, 91.8% (45/49) for adnexitis, 95.2% (20/21) for infections of the external genital organs and 86.2% (25/29) for other infections. 4. Side effects were observed in 7 of the 262 patients: eruption in 6 cases, itching in 2, diarrhea in 1. Abnormal laboratory test values were noted in 9 of the 256 patients. Most of them were slight elevation of hepatic function values. CZON showed satisfactory clinical efficacy and potent antibacterial activity, hence it appears that CZON will be a very useful antibiotic for obstetric and gynecologic infections.     

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.     

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

Fundamental and clinical studies were performed on ceftazidime ( CAZ ), a new cephem antibiotic. Following a single intravenous administration of 1 g dose of CAZ , the transfer of CAZ to the internal genital organs was good. The transfer of CAZ to retroperitoneal fluid was excellent. In a clinical trial, CAZ was given to 6 patients with obstetrical and gynecological infections. The efficacy was evaluated as excellent in 3 cases and good in the other 3 cases. No adverse effects were observed in any of the patients treated with CAZ .     

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

Fundamental and clinical studies on ceftriaxone (CTRX, Ro 13-9904) were performed in the field of obstetrics and gynecology and the following results were obtained. The serum concentration was maintained at a high level to remain 22 micrograms/ml about 24 hours after intravenous injection with 1 g CTRX. The level in each tissue except myometrium reached a peak of 50 micrograms/g or higher at 54 minutes after intravenous injection with 1 g CTRX. The peak level in the dead space exudate, obtained 4 to 6 hours after intravenous injection was 77 micrograms/ml with 1 g, and 125 micrograms/ml and 115 micrograms/ml with 2 g. The clinical efficacy was observed in all the cases (excellent in 1 and good in 3) consisting of 1 with Bartholin's abscess, 2 with adnexitis and 1 with pelvioperitonitis. Neither adverse reaction nor posttreatment laboratory test abnormality was observed in any case.