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

Ceftriaxone (Ro 13-9904, CTRX), 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 CTRX into intrapelvic genital organs were good. The peak serum level in the uterine artery after a single intravenous injection and that after an intravenous drip infusion for 30 approximately 60 minutes, both with 1 g, were 162.5 micrograms/ml and 84.4-93.8 micrograms/ml, respectively. High concentrations were obtained also in genital organ tissues; the maximum concentration was 93.8 micrograms/g by intravenous injection and 56.3-59.4 micrograms/g by intravenous drip infusion. Changes in the tissue concentration were similar to those in the serum, the level over MIC80 against main pathogenic organisms being maintained for a long time. The penetration of CTRX into intrapelvic dead space exudate was good. The level reached a peak of 18.8 micrograms/ml 2 hours after an intravenous injection with 1 g and 13.3 micrograms/ml after 12 hours, while the level over MIC80 against main pathogenic organisms was maintained for a long time. CTRX was effective in 15 out of 16 cases (93.8%) with gyneco-obstetric infections such as intrauterine, intrapelvic, adnexal infections, and postoperative would infections, administered with 1 g twice a day. No side effects were observed.     

Fundamental study on tissue distribution of ceftriaxone in the field of obstetrics and gynecology

Fundamental study on tissue distribution of ceftriaxone (Ro 13-9904, CTRX), a new cephalosporin parenteral antibiotic, was studied and the following results were obtained. CTRX had been administered by intravenous drip infusion with 1 g to 9 cases who received simple total hysterectomy. The level of CTRX in the cubital venous serum and uterine arterial serum was determined as well as the tissue concentration in the oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis. The level in the oviduct and portio vaginalis was generally high, although it was observed only in a few cases. The variation of the level in the myometrium was large. CTRX is expected to be clinically useful considering the fact that its half-life time is 8.5 hours, which is longer than that of existing cephalosporin antibiotics.     

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.     

Fundamental and clinical studies of cefpiramide in the field of obstetrics and gynecology

Cefpiramide (CPM, SM-1652), a new cephem antibiotic, was fundamentally and clinically studied. The following results were obtained. Serum and internal genital tissue levels of CPM were measured following intravenous drip infusion of 1 g. High serum levels of 30 micrograms/ml and tissue levels of more than 4 micrograms/g were at least maintained for 8 hours. Favourable transfer of CPM into the pelvic dead space exudate was observed. The exudate level was 7.25 micrograms/ml on average even at 8 hours after intravenous drip infusion. A total of 6 cases comprising 4 with Bartholin's cyst, 1 with pelvic peritonitis and 1 with lymphocyst was treated with CPM at a dose of 0.5-2 g twice daily by intravenous injection or intravenous drip infusion. The clinical response was excellent in 1 case and good in 5 cases. Side effects and abnormal laboratory findings due to the drug were not noted.     

Clinical and pharmacokinetics studies of ceftriaxone upon 2g once daily administration in respiratory tract infections

Clinical studies on ceftriaxone (CTRX) were conducted with 2 g once daily administration to respiratory tract infections. In addition, CTRX concentrations in serum, sputum and urine were determined. The results obtained are summarized as follows: 1. Clinical responses to CTRX in a total of 29 cases with respiratory tract infections were excellent in 7 cases, good in 13, fair in 8 and poor in 1 with a response rate of 69.0%. 2. CTRX concentrations in serum, sputum and urine (total and free body) were determined in 3 cases after intravenous drip infusion of 2g CTRX. Peak levels in sputum were 2.6 to 7.8 micrograms/ml, and CTRX maintained high sputum levels for 12 to 24 hours after administration.     

Free concentration and protein binding of ceftriaxone]

Ceftriaxone (CTRX) was administered in dose of 1 g 30 minutes intravenous drip infusion to 5 healthy volunteers. Cefpiramide (CPM) and cefotetan (CTT) were administered as control antibiotics. The serum concentrations of total and free drugs, using ultrafiltration, were assayed by bioassay and HPLC. Protein binding rates and pharmacokinetic parameters were calculated. Free concentration of antibiotics were following orders in each sampling time: CTRX greater than CTT greater than CPM. Mean free concentrations of CTRX at 0 hour and at 8 hours after intravenous drip infusion was more than 20 micrograms/ml and more than 2 micrograms/ml. Even at 24 hours after intravenous drip infusion free concentrations of CTRX were detectable. Mean half life in beta phase by HPLC was following orders: CTRX (7.5 hours) greater than CPM (5.4 hours) greater than CTT (4.7 hours). Mean protein binding rates were following orders: CPM (98%) greater than CTT (94%) greater than CTRX (92%). Conclusions: Characteristic of CTRX is high free drug concentration and long half life.     

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.     

Bacteriological, pharmacokinetic and clinical evaluations of ceftriaxone in the pediatric field. Pediatric study group of ceftriaxone

Ceftriaxone (CTRX), a new injectable cephem antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in the pediatric field by a study group organized with pediatricians from all over the country. The following are a summary of the results of the evaluation. Antibacterial effects: The inhibition of growth was attained for over 90% of strains of K. pneumoniae, H. influenzae and Salmonella spp. at the concentration of 0.10 micrograms/ml and of strains of S. pneumoniae and E. coli at the concentration of 2.0 micrograms/ml. The CTRX was proved to have excellent antibacterial effects. Absorption and excretion: Thirty minutes after one shot intravenous administration with 10, 20, 40 and 50 mg/kg of CTRX, its serum levels were 73, 124, 169 and 190 micrograms/ml, respectively, a clear tendency of dose-response relationship being noticed. The serum levels decreased only gradually and stayed as high as 10 to 20 micrograms/ml even after 12 hours. The half-lives of the drug were 5.5, 6.3, 6.0 and 4.7 hours for the 4 different dose levels, respectively. Following the intravenous injection with 10, 20 and 40 mg/kg, the urinary excretion rates were 55, 52 and 54%, respectively. Following the one shot intravenous administration or by the drip infusion for 30 minutes with about 50 mg/kg, CTRX levels in the cerebrospinal fluid ranged from 1 to 20.3 micrograms/ml in case of purulent meningitis (5 to 10 micrograms/ml in most cases). Clinical results: A total of 322 cases was enrolled. The efficacy of CTRX was evaluated in 295 cases out of the 322, excluding drop-outs and the cases which did not meet the protocols. The clinical efficacy rate was 94% of 191 cases where the causative bacteria were identified, CTRX being "excellent" in 108 cases and "effective" in 72. In the remaining 104 cases where the causative bacteria were not identified, the efficacy rate was 92%, CTRX being "excellent" in 42 cases and "effective" in 54. Furthermore, the efficacy rate was 89% of 18 cases infected with more than one kind of bacteria. The drug showed "excellent" or better effectiveness in 88% of 75 cases which had not responded to other antibiotics. Bacteriologically, 174 out of 216 strains (93%) which were judged to be causative bacteria disappeared with the use of CTRX. Eighty-five percent of 53 strains which had not responded to other antibiotics disappeared by the CTRX treatment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic and clinical studies on ceftriaxone in the perinatal period

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

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.     

Evaluation on ceftriaxone administered intravenously in neonates

Ceftriaxone (CTRX) was clinically evaluated and its pharmacokinetics studied in neonates. The results obtained are summarized below. 1. Blood levels of CTRX at 8 to 12 hours after intravenous injection with a single dose of 10 to 20 mg/kg ranged from 14.9 to 32.8 micrograms/ml, while T1/2 ranged from 8.2 to 24.8 hours. 2. Blood levels of CTRX at 11 hours after the completion of drip infusion which lasted one hour with a dose level 10 to 20 mg/kg, ranged from 10.6 to 25.0 micrograms/ml, while T1/2 was 5.4 to 22.8 hours. 3. Multiple intravenous administrations were given to premature infants, but blood levels did not show evidence of drug accumulation. 4. Urinary excretion in 6 hours after an intravenous injection or a drip infusion with 10 approximately 20 mg/kg of CTRX ranged from 13.8 to 58.5% of the dosage. 5. The subjects in this study were 9 neonates with suspected sepsis, pneumonia, Staphylococcus epidermidis or Staphylococcus aureus infections (sepsis, staphylococcal scalded skin syndrome, pneumonia), acute bronchitis or meconium aspiration syndrome. Efficacies CTRX were excellent or good in all these cases administered in a daily dose of 19.5 to 41.6 mg/kg for 4 to 11 days. 6. No general side effects or abnormalities were observed in blood count, or hepatic or renal function.     

Clinical studies and sputum levels of ceftriaxone once daily administration in respiratory tract infection

Ceftriaxone (CTRX), a new cephalosporin, was investigated by once daily administration for its clinical efficacy and safety on respiratory tract infections. The results obtained are summarized as follows: 1. Clinical responses to CTRX of a total of 39 cases with respiratory tract infections were excellent in 12 cases, good in 23, fair in 3, poor in 1 with an efficacy rate of 89.7%. Against acute bronchitis, lung abscess, bronchiectasis, chronic bronchitis and obstructive pneumonia, efficacy rates were 100%. 2. Serum levels and urinary excretion rates of CTRX were investigated in 2 cases after intravenous drip infusion of the drug at doses of 1 g and 2 g, respectively. Although urinary excretion rate tended to decrease with the deterioration of renal functions, prolongation of serum half-life was slight in those patients with normal liver function. In 1 case, it remained at 1.9 micrograms/ml at 12 hours and in another at 0.9 microgram/ml at 22 hours in sputum. According to the results, it appears that once daily administration of CTRX is effective and well tolerated in patients with acute respiratory infections.     

Pharmacokinetic and clinical evaluations of ceftriaxone in perinatal infections in obstetrics and gynecology

Ceftriaxone (CTRX), an injectable cephem antibiotic agent, was studied for its pharmacokinetic properties and clinical usefulness in perinatal infections in obstetrics and gynecology on a multicenter basis. The study results are summarized below. 1. Following the one-shot intravenous injection of CTRX 1 g to pregnant women before labor, the maternal serum level of CTRX reached a peak at 131.8 micrograms/ml soon after the injection then it began to decrease gradually. T 1/2 was 6.7 hours. The umbilical serum level reached a peak at 16.0 micrograms/ml at 4.9 hours post-dose and decreased gradually with a half-life of 8.1 hours. The umbilical serum level was higher than the maternal serum level at about 12 hours post-dose. The amniotic fluid level reached a peak of 9.6 micrograms/ml at 12.8 hours post-dose. T 1/2 was 15.2 hours. The amniotic fluid level at about 15 hours post-dose or later exceeded the maternal serum level and was almost equal to the umbilical serum level at 24 hours post-dose. 2. Clinical usefulness was evaluated in 79 evaluable cases out of 89 treated for various infections at puerperium or for prophylaxis of infections at cesarean section or premature rupture of membranes (PROM). The efficacy rate was 100% in 7 cases of prenatal infections such as urinary tract infection and 30 cases of postnatal infections such as puerperal intrauterine infections. In 42 cases treated for prophylaxis in cases of cesarean section or PROM, the efficacy rate was 92.9%. Bacteriologically, 29 strains of pathogens were isolated from 26 cases. The disappearance rate of the pathogens was 96.0% as 23 strains were eradicated, 1 strain was substituted and no change was observed in 1 strain with unknown results in 4 strain. Skin rash and itching appeared in 1 patient as an adverse effect (1.1%). There were 10 cases of abnormal clinical laboratory test results such as elevated transaminase level were observed in 7 patients (7.9%). From the results, CTRX was considered to be a useful drug for the perinatal infection in the obstetrics and gynecology fields.     

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

It is reported that ceftriaxone (Ro 13-9904, CTRX) has a half-life time of 7 to 8 hours. In the present study, the serum level 18 hours after intravenous injection with 1 g CTRX was as high as 9.3 micrograms/ml while obviously a higher tissue concentration was maintained compared with other drugs. These facts suggest that CTRX is effective against infections and that the dosage and frequency of administration could be reduced. The global evaluation revealed that CTRX was clinically effective in all the 4 cases with infections. As the adverse reaction, light leukopenia was observed only in 1 case out of the present 4 cases and 20 others administered with CTRX.     

Clinical evaluation of ceftriaxone in the pediatric field

Ceftriaxone (Ro 13-9904, CTRX), developed by F. Hoffmann-La Roche Ltd. in Switzerland, was used for the pediatric infections and the following results were obtained. The mean blood level of CTRX in 2 children after a 60-minute intravenous drip infusion with 20 mg/kg was 58.6 micrograms/ml at 30 minutes, 75.0 micrograms/ml at 1 hour, 39.85 micrograms/ml at 2 hours, 27.74 micrograms/ml at 4 hours, 20.71 micrograms/ml at 6 hours, 11.72 micrograms/ml at 12 hours and 3.91 micrograms/ml at 24 hours while the half-life time was 5.9 hours in one child and 7.6 hours in the other. CTRX was used in 22 children with acute infections consisting of 3 with acute pharyngeal tonsillitis, 4 with acute bronchitis, 8 with bronchopneumonia, 6 with infections of skin soft tissue and 1 with salmonellosis. The results were excellent in 5 cases and good in 17, indicating an efficacy rate of 100%. Out of 10 cases where the causative strains were detected, 4 cases were followed about the activities of the respective bacteria, i.e., H. influenzae, Streptococcus group A, S. aureus and Salmonella group B, all of which were eradicated after the end of administration. The daily dose of CTRX ranged from 30 to 50 mg/kg and generally a larger dose was used for serious infections. CTRX was administered twice daily in 20 out of 22 cases, by an intravenous injection in 4 and an intravenous drip infusion in 18, for 2 to 4 days in 16 and 5 to 8 1/2 days in 6. No clinical adverse reactions were observed while the laboratory test found a slight elevation of GOT in one and that of GOT and GPT in another. From the above results, CTRX was judged to be a highly useful drug for treatment of pediatric infections.     

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.     

Clinical evaluation of ceftriaxone in the field of gynecology

Ceftriaxone (Ro 13-9904, CTRX) was administered to 3 cases with gynecological infections and following results were obtained. CTRX was administered by intravenous drip infusion or intravenous injection with 2 g per day for 4 to 6 days. The clinical efficacy was good in all cases (2 cases with pyometra, 1 case with adnexitis and endometritis). No side effect could be determined in all cases.     

Fundamental study on ceftriaxone

Ceftriaxone (CTRX) was examined in the blood level and urinary excretion between a healthy group of 2 persons receiving 1 g CTRX for 1 day and the other of 3 patients with renal failure receiving 1 g for 3 days, both by intravenous injection or intravenous drip infusion. In the healthy group, the blood half-life time of CTRX was 6.0 hours in 1 person and 8.2 hours in the other, being 7.1 hours on average. The mean blood level in the healthy group was 199 micrograms/ml at peak and was 13 micrograms/ml at 24 hours after administration. In patients with renal failure, the peak blood level ranged from 136.8 to 161.1 micrograms/ml on the 1st day, from 163.1 to 217.0 micrograms/ml on the 2nd day and from 156.4 to 189.7 micrograms/ml on the 3rd day, showing no tendency of getting higher, while the bottom level did from 15.2 to 47.4 micrograms/ml on the 1st day, from 23.3 to 67.9 micrograms/ml on the 2nd day and from 10.9 to 72.6 micrograms/ml on the 3rd day. The urinary excretion rate was 54.6 +/- 3.7% on average in the healthy group while it ranged from 13.7 +/- 1.8 to 27.9 +/- 7.9% in the patient group. CTRX was effective especially against E. coli among the strains clinically isolated from the patients with renal failure. No side effects were observed in any case.     

Pharmacokinetic study of cefsulodin in children

Cefsulodin (CFS), a cephem antibiotic, was administered to 26 children aged from 11 months to 11 years by intravenous injection or intravenous 1-hour drip infusion in doses of 15 and 50 mg/kg body weight to investigate serum and urinary concentrations. The following results were obtained. Serum concentration The serum concentrations of CFS at 5 minutes after intravenous injection of 15 and 50 mg/kg were 57.1 and 224.2 micrograms/ml, respectively. The biological half-lives (T 1/2 beta) were 1.28 and 1.12 hours. The serum concentration of CFS after intravenous 1-hour drip infusion reached a peak at the end of infusion, i.e. 29.9 micrograms/ml for 15 mg/kg and 121.9 micrograms/ml for 50 mg/kg, and T 1/2 beta were 1.22 hours for 15 mg/kg and 1.27 hours for 50 mg/kg. The AUC was proportional to the doses for both intravenous injection and intravenous drip infusion. The serum clearance was about twice the value in adults and the distribution volume was about 1.5 times as large. Urinary excretion The urinary excretion up to 6 hours after administration was: 69.0% for 15 mg/kg and 61.9% for 50 mg/kg in cases of intravenous injection, and 62.4% for 15 mg/kg and 71.1% for 50 mg/kg in cases of intravenous 1-hour drip infusion. The percent urinary excretion was similar to that in adults.     

A clinical trial of astromicin, a new aminoglycoside antibiotic, in thoracotomized patients and astromicin concentrations in the lung tissue

There have been no report on concentrations in human lung tissue of aminoglycoside antibiotics which are frequently used in combination with cephem antibiotics in the treatment of severe respiratory infections. The authors examined lung tissue concentration of astromicin (ASTM) during clinical trials in thoracotomized patients using intravenous drip infusion just before operation. And the following conclusions have been obtained: 1. The average peak serum level obtained upon intravenous drip infusion of ASTM 200 mg for 1 hour just before operation was 11.2 micrograms/ml at 1 hour after starting the administration and half-life of ASTM in beta phase was 2.90 hours. 2. ASTM concentrations in the lung tissue upon 1 hour intravenous drip infusion just before operation at a dose level of 200 mg reached a maximum at 2 hours after the start of the administration averaging 7.7 micrograms/ml and were 27.7-68.8% of serum peak level. 3. Bronchiolar concentrations of ASTM 200 mg upon 1 hour intravenous drip infusion just before operation were 33.0-72.3% of peak serum level. These concentrations appear to be sufficient for the treatment of target infections. 4. The 1 hour intravenous drip infusion of ASTM 200 mg appeared to be clinically safety and useful as was the intramuscular injection of ASTM 200 mg.