Fundamental and clinical studies of ceftizoxime suppositories in the pediatric field

The fundamental and clinical studies of ceftizoxime suppository (CZX-S) in the field of pediatrics were made, with the following results. The serum concentration of CZX in the CZX-S 250 mg-administered group peaked 6.00-22.5 micrograms/ml during the period of 15 minutes to 1-hour after dosing, and gradually declined thereafter. The half-life was 1.37-3.81 hours. In the CZX-S 125 mg-administered group, the serum concentration peaked 2.25-21.0 micrograms/ml at 15-30 minutes after dosing and decreased with time. The half-life was 0.95--1.84 hours. The 6-hour urinary recovery rate of CZX in the CZX-S 250 mg group was 22.0-47.5%. The 6-hour urinary recovery rate in the CZX-S 125 mg group was 17.2-25.3%. CZX-S was given 12-73 mg/kg/day (divided into 1-3 times) to 7 children with respiratory tract infection etc. who were considered to respond well to the drug. The clinical effectiveness rate was 100% inclusive of "excellent" and "good". The side effect of pain on insertion was encountered in 1 child.     

Fundamental and clinical studies of ceftizoxime rectal suppositories in the field of pediatrics

This paper deals with fundamental and clinical results, in the field of pediatrics, of the newly developed rectal suppository (CZX-S) of a cephem antibiotic ceftizoxime (CZX). CZX-S was well absorbed in children. The mean peak serum concentrations of CZX in the 125 mg-administered group (average: 9.9 mg/kg) and the 250 mg-administered group (average: 13.4 mg/kg) were 5.10-7.71 micrograms/ml at 15-30 minutes after dosing. Serum concentrations of CZX were measurable level in almost all the children at 6 hours after administration with the half-lives were 1.34-1.55 hours. The 6-hour urinary excretion rate accounted for 16.5-22.0%. CZX-S was administered to 30 children with acute upper or lower respiratory tract infections about 20-60 mg/kg/day in 3-4 divided portions. CZX-S provided favorable therapeutic-effect in most of the children 3-5 days after administration. The effectiveness rate was 93%. The causative organisms of H. influenzae (3 cases) and S. aureus (4 cases) isolated clinically from pharyngeal mucous and sputum were eradicated after administration of CZX-S. Anal pain and diarrhea experienced in 5 of the 30 children and CZX-S was withdrawn in 4 (of the 5) children, but exhibited satisfactory therapeutic-effect in 2 of the 4 cases up to withdrawal of the drug. An increase in GOT and GPT was observed in 3 cases. The values returned to the normal range in 1 case after the treatment with CZX-S. The test was not reexamined in the other 2 cases. The present clinical result suggests the usefulness of CZX-S substituted for oral and injectable forms in the treatment of various pediatric infections caused by organisms sensitive to CZX.     

Clinical investigation of ceftizoxime sodium suppositories in pediatric infections

Ceftizoxime suppository (CZX-S) was given to 6 patients, with the following results. The peak serum concentration of CZX was 1.8-7.5 micrograms/ml at 30 minutes after dosing of CZX-S with 9.6-16.7 mg/kg. The antibacterial activity of CZX revealed that the drug can be expected to be effective sufficiently. The overall effect of CZX-S was "markedly improved" in 1 and "moderately improved" in 3 of the 4 patients with pneumonia and "markedly improved" in 1 and "slightly improved" in 1 of the 2 with UTI. CZX-S caused a slight increase in frequency of defecation in 2 of the 6 patients. There were no abnormal findings of symptoms or laboratory test values which were ascribable to side effects.     

Study on tissue transfer of ceftizoxime suppository in the field of obstetrics and gynecology

A pharmacokinetic study on ceftizoxime suppository (CZX-S), a new rectal suppository of ceftizoxime (CZX), was carried out in the field of obstetrics and gynecology. Concentrations of CZX after single rectal administrations of a 500 mg dose in peripheral venous serum, uterine arterial serum and internal genital organs of 15 patients who received simple panhysterectomy were examined. Peak levels of CZX in peripheral venous serum were 7.26 to 8.88 micrograms/ml at 30 minutes after the administration. Concentrations of CZX in internal genital organs reached 2.12 to 8.96 micrograms/g at 30 minutes after the administration and then decreased slowly, but still remained at 0.37-3.12 micrograms/g after 4 hours.     

Pharmacokinetics of ceftizoxime suppository in experimental animals

Ceftizoxime suppository (CZX-S) was administered rectally to mice, rats and dogs, and the pharmacokinetics were studied in comparison with those after intravenous, intramuscular and subcutaneous administration of ceftizoxime (CZX). Absorption of CZX given rectally was rapid in all animals, similar to intramuscular or subcutaneous administration. The peak serum levels of CZX in mice, rats and dogs when administered rectally at a dose of 25 mg/kg were 23.1 micrograms/ml at 7.5 minutes, 23.5 micrograms/ml at 15 minutes and 25.2 micrograms/ml at 15 minutes, respectively. These values were about 76%, 68% and 42% of the values for subcutaneous or intramuscular administration in mice, rats and dogs at the same respective doses. Urinary recoveries of CZX after rectal administration of 25 mg/kg were 44.2% (0-12 12 hours) in rats and 27.7% (0-6 hours) in dogs, and 2.7% (0-6 hours) of the dose was excreted into bile fluid in rats. Organ distribution of CZX when administered rectally to rats was similar in distribution pattern to that of muscular administration, although its concentrations in various organs were slightly lower than those for intramuscular administration, as was the case for serum concentration. Serum concentrations of CZX were proportionately elevated with dose when dogs were rectally administered CZX-S in doses of 12.5, 25 and 50 mg/kg. In the case of multiple administrations (t.i.d. for 10 days) of CZX-S to dogs, no remarkable difference was found in serum concentrations of CZX in comparison with single doses, and no accumulation of CZX was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical studies of ceftizoxime suppositories in respiratory tract infections and urinary tract infections in children

A fundamental and clinical study of ceftizoxime (CZX) suppositories was performed in pre-school and school-age children. The average time courses of CZX serum and urinary concentrations after administration of CZX suppository 250 mg (i.e. per kg body weight doses of 8.3-10.9 mg) to 4 school-age children were as follows. Serum concentrations: 6.1 micrograms/ml at 15 minutes, 6.3 micrograms/ml at 30 minutes, 3.8 micrograms/ml at 1 hour, 1.7 microgram/ml at 2 hours, 0.5 microgram/ml at 4 hours and 0.2 microgram/ml at 6 hours with a biological half-life of 1.43 hours. Urinary concentrations: 885 micrograms/ml for 0-2 hours, 209 micrograms/ml for 2-4 hours and 112 micrograms/ml for 4-6 hours with an average 6-hour urinary recovery rate of 25.6%. The clinical and biological effectiveness and adverse reactions were studied in 11 infants and school-age children afflicted with various infections (acute purulent tonsillitis, 1; acute bronchitis, 3; acute pneumonia, 4; and UTI, 3). The clinical responsiveness was "excellent" in 8, "good" in 2, and "failure" was recorded in 1, with an overall efficacy of 90.9% inclusive of "excellent" and "good". The microbiological effectiveness of CZX suppositories on presumed pathogenic organisms comprising 4 strains of H. influenzae, 1 strain of H. parainfluenzae, and 3 strains of E. coli was satisfactory, as evidenced by the substantially high eradication rate of 87.5%. The only organism that survived CZX suppository treatment was 1 strain of H. influenzae which however was greatly decreased. The only side effect was diarrhea in 1 patient, which however did not necessitate withdrawal of the drug. The only laboratory test abnormality was GOT and GPT elevation in 1 patient which was normalized within 8 days. In conclusion, CZX suppositories were found to be efficacious and safe for treatment of bacterial infections in children.     

The clinical evaluation of ceftizoxime suppositories in the pediatric field

Clinical evaluation of ceftizoxime suppository (CZX-S), a new antibiotic rectal suppository, was performed in 5 cases with bacterial infections in pediatric field (2 with acute bronchitis, 1 with acute tonsillitis, UTI and pertussis, respectively) and the following results were obtained; Blood levels of CZX at 10-20 minutes after administration of CZX-S at a dose of 10.0-26.3 mg/kg in 5 cases were 3.26-23.3 micrograms/ml and the urinary excretion rates within 6 hours were 15.2, 60.1, 60.2% in 3 of 5 cases measured respectively. Clinical effects were excellent in 3 and good in 2 cases. Slight elevation of GOT and GPT was observed in 1 case. No other side effects were observed. The patients' tolerability against rectal suppository was good. From the above results, we concluded that CZX-S is useful for treating the pediatric patients with various infections.     

Basic and clinical studies of ceftizoxime suppositories in the pediatric field

A bacteriological and clinical study of ceftizoxime suppositories (CZX-S) let to the following results. The CZX serum concentration 10 minutes after insertion of one 250 mg suppository (i.e. 5.7-15.2 mg CZX per kg body weight) ranged from 1.64 to 6.53 micrograms/ml (average: 4.41 micrograms/ml). In one child the concentration 7 minutes after insertion was 4.13 micrograms/ml. Therapeutic responsiveness was recorded as "effective" in 8 (88.9%) of the 9 children who were broken down into 6 with tonsillitis, 1 with pharyngitis, and 2 with UTI. Bacteriological studies conducted in 5 children have confirmed eradication in 4 children, one of whom showing appearance of another strain. The rate of discharge of the suppository within 10 minutes after insertion was 20.4%. Reddening and erosion of the anus were observed in 1 child.     

Clinical investigation of ceftizoxime sodium suppositories in the field of pediatrics

The clinical study of CZX-S in the field of pediatrics was performed and the following results were obtained. The overall effect of CZX-S was "markedly improved" in 2 and "moderately improved" in 4 of the 6 patients with bacterial infection. Bacteriological findings show that causative organisms were eradicated in all the 5 patients observed. The breakdown of the organisms was S. aureus, S. pyogenes, S. pneumoniae, H. influenzae and E. coli. The serum concentration of CZX was 3.3 approximately 15.4 micrograms/ml (mean +/- S.E. 8.9 +/- 2.0 micrograms/ml) at 15-37 minutes after initial rectal administration with CZX-S 125 (dose: 7.7-11.9 mg/kg). While, in the CZX-S 250 administratered group, the serum concentration was 3.1 micrograms/ml and 10.5 micrograms/ml at 20 minutes after initial rectal administration (dose: 5.6 mg/kg and 14.7 mg/kg). The urinary recovery rate up to 6 hours after initial rectal administration was 68.6% in 1 patient given CZX-S 125 and 28.3-52.5% (mean +/- S.E. 38.7 +/- 7.2%) in 3 patients given CZX-S 250. Side effects and abnormalities in laboratory test values were not observed in any cases.     

Laboratory and clinical studies on ceftizoxime (author's transl)

The authors have carried out the laboratory and clinical studies of ceftizoxime (CZX), and obtained the following results. 1. The antibacterial activities of CZX were measured by plate dilution method against clinical isolates of S. aureus, E. coli, K. pneumoniae and P. aeruginosa. CZX inhibited the growth of S. aureus at concentrations less than 12.5 micrograms/ml, and the peak of sensitivity distribution was obtained at 3.13 micrograms/ml with an inoculum size of 10(6) cells/ml. And the peak sensitivity distribution of E. coli and K. pneumoniae were obtained at less than 0.1 microgram/ml and that of P. aeruginosa was obtained at 6.25 micrograms/ml. 2. Phagocytosis was determined by Quie's method. Phagocytosis of E. coli and K. pneumoniae by human polymorphonuclear neutrophil was more enhanced in the presence of 1 MIC and 1/2 MIC of CZX than of CEZ at 4 and 6 hours after incubation. 3. As for pharmacokinetic study, CZX was given by intravenous injection and drip infusion for 1 hour at a single dose of 10 mg/kg and 30 mg/kg. After intravenous injection of 10 mg/kg and 30 mg/kg of CZX, the mean peak serum levels were 19.1 +/- 3.4 micrograms/ml and 69.1 micrograms/ml at 30 minutes, and half-life times were 1.20 hours and 1.35 hours, respectively. After 1 hour drip infusion of 10 mg/kg and 30 mg/kg of CZX, the mean peak serum levels were 28.8 +/- 3.6 micrograms/ml and 60.9 +/- 5.9 micrograms/ml at the end of infusion, and half-life times were 1.40 hours and 1.77 hours, respectively. The mean urinary excretion rates were between 75.3% and 101% up to 6 hours after intravenous injection and drip infusion. 4. CZX was given to 4 cases with tonsillitis, 3 with pneumonia, 1 with enteritis, 4 with U.T.I., totaling 21 cases. A daily dose of CZX between 350 mg and 2,000 mg was given for 3 to 5 days. Clinical results obtained were good in all cases. No side effects and abnormal laboratory findings were observed.     

Fundamental study on ceftizoxime suppositories in adults and children

The pharmacokinetics of newly developed ceftizoxime suppository (CZX-S) was studied in healthy volunteers and in children, compared with that of intramuscular CZX and intravenous CZX: In 8 volunteers (aged 19 to 24 years), each of 500 mg (potency) CZX-S containing 3%, 4% and 5% sodium caprate was compared with 500 mg intramuscular CZX and 500 mg intravenous CZX as a single administration in the cross-over method. In addition each of 500 mg CZX-S containing 4% and 5% sodium caprate was studied in 2 groups of 8 volunteers (aged 22 to 24 years) and of 8 volunteers (aged 19 to 27 years); each CZX-S was given 3 times a day successively for 5 days. The pharmacokinetics of 125 mg and 250 mg CZX-S, which contained 3% sodium caprate, were also evaluated as a single administration in 9 children (aged 6 years 4 months to 12 years 0 month) and in 11 children (aged 7 years 8 months to 12 years 4 months), respectively. The irritabilities of CZX-S were studied in all subjects who participated in this trial. The feeling of foreign body, the feeling of defecation, the burning sensation and the pain were evaluated in volunteers; the feeling of defecation and the pain were evaluated in children. The results were as follows: I. Pharmacokinetics in healthy volunteers 1. Given as a single administration The mean peak concentrations of serum CZX were occurred 30 minutes after 500 mg CZX-S containing 3%, 4% and 5% sodium caprate, which were 10.5 mcg/ml, 12.3 mcg/ml and 12.4 mcg/ml, respectively. These values were 1.35 mcg/ml, 1.60 mcg/ml and 1.69 mcg/ml at the conversion unit of 1 mg dose per 1 kg body weight. The mean peak serum CZX concentration of CZX-S containing 3% sodium caprate was slightly lower than that of CZX-S containing 4% or 5% sodium caprate, but was 1.9 times higher than that of the ABPC suppository. There was no marked difference among 3 preparations of CZX-S in mean Tmax and T1/2. Cmax of CZX-S containing 3% sodium caprate was 1.40 mcg/ml at the conversion unit of 1 mg/kg. AUC of CZX-S containing 3% sodium caprate was slightly smaller than that of CZX-S containing 4% or 5% sodium caprate, but 3.1 times that of the ABPC suppository in healthy volunteers. When 500 mg CZX was intramuscularly administered by one shot to 8 volunteers, Tmax was same as that of CZX-S or was slightly later.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical study of ceftizoxime suppositories in acute suppurative otitis media in children and tissue concentration of ceftizoxime in the palatine tonsil after administration of ceftizoxime suppositories

The newly developed ceftizoxime rectal suppository (CZX-S) contains 125 mg or 250 mg ceftizoxime (CZX) in potency. From the laboratory and clinical studies on CZX-S, the following results were obtained. Concentration of CZX in serum and palatine tonsil when 250 mg of CZX-S was rectally administered reached the peak level rapidly. The serum levels were 9.39 micrograms/ml in 30 minutes, 6.00 micrograms/ml in 45 minutes, 4.55 micrograms/ml in 60 minutes, 3.87 micrograms/ml in 90 minutes and 2.65 micrograms/ml in 120 minutes. The palatine tonsil levels were 2.73 micrograms/g in 30 minutes, 1.83 micrograms/g in 45 minutes, 1.54 micrograms/g in 60 minutes, 0.99 micrograms/g in 90 minutes and 0.74 micrograms/g in 120 minutes. About 30% of serum concentrations were distributed into palatine tonsil. CZX-S was administered at a daily dose of 375 mg or 750 mg divided 3 times for 4 approximately 9 days in 19 cases of acute suppurative otitis media of children. The overall clinical effect was excellent in 7 cases, good in 7 cases, fair in 2 cases and poor in 3 cases. The effectiveness rate was 73.7%. No side effects were observed in any cases.     

Effects of ceftizoxime suppository rectal dosing on cecal microflora in mice

The effect of ceftizoxime suppository (CZX-S), a new rectal preparation of ceftizoxime (CZX), against cecal microflora of mice following consecutive rectal administration was compared with that after subcutaneous administration of CZX. The numbers of aerobic and anaerobic bacteria except Enterobacteriaceae of cecal microflora were not markedly changed by the rectal administration of CZX-S at a dose of 25 mg/kg 3 times daily for 10 days. Although the number of Enterobacteriaceae was decreased, recovery was rapidly observed after completion of the administration period. In the case of subcutaneous administration, a decrease in Enterobacteriaceae was also observed, but this was no more remarkable than that occurring with rectal administration. Moreover, effects on the state of feces, i.e., diarrhea, were not observed in any of the mice. The peak level of CZX in the cecum contents when administered rectally at a dose of 25 mg/kg was 13.8 micrograms/g at 4 hours, while it was less than the determination limit (2.0 micrograms/g) when administered subcutaneously at the same dose.     

Pharmacokinetic and clinical studies of ceftizoxime in newborn infants

Pharmacokinetic and clinical studies of ceftizoxime (CZX) were performed in infants given intravenously. The obtained results are summarized as follows. 1. Serum concentrations of CZX in 2 and 3 day-old mature infants given 20 mg/kg by one shot intravenous injection peaked at 49.0 and 57.9 micrograms/ml in 1 hour and decreased to 14.4 and 24.9 micrograms/ml in 8 hours after dosing, respectively. Half-lives were 3.9 and 5.6 hours, respectively. In 5 day-old or older mature infants, peak serum levels ranged from 20.9 to 38.0 micrograms/ml at 1 hour after the injection. Levels of CZX at 8 hours after injection were 1.31 to 7.32 micrograms/ml. Half-lives were 1.6-3.0 hours in all the infants except one. 2. In a 3 day-old premature infant given the same dose by a bolus intravenous injection, the serum level peaked at 45.7 micrograms/ml in 1 hour after the injection. The level at 8 hours after injection was 15.7 micrograms/ml. The half-life was 4.2 hours. In 5-15 day-old premature infants, half-lives were 2.3-3.1 hours in all the infants except one. 3. Serum concentrations of CZX in 1 and 2 day-old infants given 20 mg/kg by intravenous drip infusion peaked at 49.4 to 115.0 micrograms/ml in 1 hour after dosing. Half-lives were rather long, 4.0 and 5.1 hours, in the 2 infants. 4. Peak serum levels and half-lives tended to be lower and shorter in 5 day-old or older ones than in the 3 day-old or younger infants. 5. No changes in the serum concentration were observed even after dosing with 20 mg/kg of continuous one shot intravenous injection. 6. Urinary recovery rates during the first 8 hours (one is 6 hours, two is 9 hours) after 20 mg/kg intravenous bolus injection of CZX tended to be lower in 3 day-old or younger infants than in 5 day-old or older infants. 7. Eleven infants with various bacterial infections were given CZX by intravenous bolus injection or drip infusion. Dosage of CZX used in the present study were 36-148 mg/kg/day in 2-3 divided doses. Duration of treatment ranged from 3 to 12 days. Clinical efficacy of CZX was excellent or good in all the infants with acute bronchitis, acute pneumonia, suspected sepsis infected in uterine, acute otitis media, cellulitis, meningitis caused by Klebsiella pneumoniae and Escherichia coli, acute urinary tract infection and periproctic abscess except 1 case of acute bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and pharmacokinetic evaluations of ceftizoxime suppositories in children

Ceftizoxime suppository (CZX-S) was evaluated for its safety, clinical efficacy and pharmacokinetics in pediatric patients. The Cmax, 4.8 to 9.5 micrograms/ml, was obtained 15 to 30 minutes after administration of CZX-S, and the serum half-life was 0.93 hour. Cross-over comparison with intramuscular CZX in a child showed approximately one-third bioavailability of the suppository against intramuscular injection. CZX-S was effective in all the 26 bacterial infections including acute pharyngitis, pneumonia, soft tissue infection, and urinary tract infections. The causative organisms were eradicated in 95%. Mild diarrhea (17%) was the only side effect observed in the study. The data suggest that CZX-S is an excellent alternative to oral and injectable antibiotics for the treatment of mild to moderate bacterial infections due to the susceptible organisms.     

Fundamental and clinical studies on ceftizoxime suppositories in children

The peak levels of serum ceftizoxime (CZX) after a single rectal administration of CZX-S at doses of 125 and 250 mg in 157 pediatric patients were occurred at 21 approximately 25 minutes in pediatric patients aged less than 1 year and over than 7 years, at 16-20 minutes in 1-3 years patients, at more than 26 minutes in 4-6 years patients. They were 9.45, 9.58, 11.71, 12.43 mcg/ml, respectively. The mean highest levels of serum CZX were 8.56, 10.66, 12.50 mcg/ml after the administration of CZX-S as less than 10.0, 10.1-15.0, 15.1-20.0 mg/kg dose respectively, all of which were occurred at 21-25 25 minutes. A close dose response was observed. The pain of insertion was not observed in any cases. The discharge of melted suppository or defecation after administration was observed in 15.2% of total 184 cases, which was noticed more frequently in the lower aged children. There was no influence by dose. Clinical effects of CZX-S were studied in 72 pediatric patients with various infections. CZX-S was administered rectally at the mean daily dose of 41.0 mg/kg divided into 3 or 4 times for 6 days. Clinical responses were excellent in 46 cases, good in 24 cases, fair in 2 cases. The efficacy rate was 97.2%. Regarding side effects, the pain of insertion was noted in 2 cases (2.8%), diarrhea in 6 cases (8.3%), the elevation of eosinophil in 1 case (1.7%). Bacteriologically, 23 strains (92.0%) out of 25 strains isolated from the patients were eradicated.     

Clinical effects of ceftizoxime suppositories in pediatric infections

A clinical trial of ceftizoxime suppositories (CZX-S) was conducted in children whose chemotherapy was considered to be best performed in this dosage form at the physician's discretion. The subjects were 5 children with infection, consisting of 2 with pneumonia, 1 with tonsillitis, and 2 with UTI. The results were as follows. The clinical response to CZX-S was "markedly effective" in 3 and "effective" in 2, with the 100% effectiveness rate. Neither adverse drug reactions nor abnormal laboratory tests were detected. No unwanted expulsion of the suppository occurred. The serum concentration of CZX 30 minutes after the first insertion ranged from 8.38 to 11.4 micrograms/ml, and the urinary concentration of CZX in the 6-hour urine collections, from 23.6 to 290 micrograms/ml.     

Pharmacokinetics of cefixime in patients with impaired renal function

Cefixime (CFIX) was given orally in a single dose of 100 mg to 7 patients with varying degrees of impaired renal function (Ccr 12.0-56.7 ml/min) and serum concentrations and urinary excretion rates were measured with time for the first 24 hours by the bioassay method to investigate in vivo pharmacokinetics of the drug. The results obtained are summarized as follows. The mean peak serum concentration of CFIX in 3 patients with moderately impaired renal function (group I: Ccr greater than or equal to 30-less than 60 ml/min) was 2.04 micrograms/ml at 6 hours after dosing and gradually declined to 0.10 microgram/ml at 24 hours after dosing. The half-life was 4.15 hours. The mean peak serum concentration of CFIX achieved was 2.27 micrograms/ml at 8 hours after dosing in 4 patients with severely impaired renal function (group II: Ccr greater than or equal to 10-less than 30 ml/min) and the concentration of CFIX was 0.99 microgram/ml even after 24 hours. The half-life was prolonged to 11.05 hours. There was no great difference between groups I and II in the first 24-hour urinary excretion rates. However, the first 4-hour urinary excretion accounted for 2.14% of the administered dose of CFIX in group I but only 0.47% in group II. Urinary concentrations of CFIX peaked at 4-6 hours after dosing in both groups, and thereafter gradually decreased in group I. Whereas, they did not decline much in group II until 24 hours after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical efficacy and pharmacokinetic evaluation of ceftizoxime in neonates and young infants

Thirteen neonates and young infants, including 5 infants with very low birth weight, were treated with ceftizoxime (CZX) and its clinical efficacy and side effects were evaluated. The ages of the patients ranged from 0 to 96 days, and their body weights ranged from 580 to 5,050 g. Doses given were 20-54 mg/kg every 6 to 12 hours for 2.5 to 7.5 days. Two infants with sepsis, one with urinary tract infection, one with sepsis and urinary tract infection, and 1 with fetal infection were considered to have responded satisfactorily to the CZX treatment. The drug was well tolerated and side effects was not apparent. Pharmacokinetic studies were done on CZX in 8 patients including 4 infants with very low birth weight. Their ages ranged from 2 to 91 days, and body weights from 545 to 5,050 g. Serum concentrations at 2 hours after single 20 mg/kg intravenous bolus injections were 19.2 to 44.2 micrograms/ml and the levels were 2.11 to 26.3 micrograms/ml at 8 hours. Elimination half-lives of CZX ranged 1.90 to 9.57 hours in these patients. In 2 infants with very low birth weights with ages 7 and 91 days, half-lives were as long as 9.57 and 8.24 hours, respectively. Urinary recovery in 6 hours was 31.9-66.9% in 5 patients. Urine concentrations of the drug in 24 samples collected at various time from the 7 patients ranged from 130 to 3,219 micrograms/ml. Influence of CZX on the fecal flora was studied in 1 patient given 20 mg/kg X 4/day of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.