Pharmacokinetic studies on oral antibiotics in pediatrics. II. A pharmacokinetic study on cefteram pivoxil in pediatrics

A pharmacokinetic study on cefteram pivoxil (CFTM-PI) granules and tablets for pediatric use was performed, and pharmacokinetic parameters were calculated using the one-compartment open model with a time lag. 1. Twelve school children were administered orally with CFTM-PI granules at a dose level of 3 mg/kg either at 30 minutes before meal or 30 minutes after meal on a crossover design, and serum concentrations and urinary excretion rates of CFTM were determined. Tmax, Cmax, T 1/2 and urinary excretion rate following the administration before meal were 1.3 +/- 0.1 hours, 1.35 +/- 0.11 micrograms/ml, 1.21 +/- 0.07 hours and 13.4 +/- 1.5%, respectively. Tmax, Cmax, T 1/2 and urinary excretion rate following the administration after meal were 2.9 +/- 0.3 hours, 1.08 +/- 0.09 microgram/ml, 1.72 +/- 0.26 hours and 23.3 +/- 2.2%, respectively. Earlier Tmax, higher Cmax and lower urinary excretion rate were observed when the drug was administered before meal than when administered after meal. 2. Six school children were administered orally with CFTM-PI granules at 30 minutes after meal at a dose level of either 3 mg/kg or 6 mg/kg on a crossover design, and serum concentrations and urinary excretion rates of CFTM were determined. Cmax at a dose level of 3 mg/kg was 1.50 +/- 0.26 microgram/ml, Cmax at a dose level of 6 mg/kg was 2.58 +/- 0.29 micrograms/ml. There existed dose response. 3. Eighteen school children, 10 younger children and 6 infants were administered orally with CFTM-PI granules at a dose level of 3 mg/kg at 30 minutes after meal, and serum concentrations and urinary excretion rates of CFTM were determined. Tmax in school children, younger children and infants were 2.8 +/- 0.3, 3.4 +/- 0.3 and 2.0 +/- 0.4 hours, respectively. Slightly earlier Tmax's were observed in infants than in other children. Cmax in school children, younger children and infants were 1.22 +/- 0.11, 1.03 +/- 0.12 and 0.94 +/- 0.15 micrograms/ml, respectively. It seemed slightly high in the older school children, younger children, infants. Although T 1/2 were nearly the same in all age groups, it seemed somewhat longer in school children than in others. Urinary excretion rates in school children, younger children and infants were 21.5 +/- 1.8, 19.3 +/- 2.0 and 7.6 +/- 0.1%, respectively. Obviously low excretion rates were observed in infants.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic, bacteriological and clinical evaluation of cefpodoxime proxetil in pediatrics

Pharmacokinetic, bacteriological, and clinical studies in pediatrics on cefpodoxime proxetil (CPDX-PR, CS-807) (pediatric dry syrup) were performed. 1. Serum concentrations and urinary excretions of CPDX after administration of CPDX-PR to children (ages between 6 and 14) were investigated. Four cases were administered with CPDX-PR at a dose level of 3 mg/kg 30 minutes before or after meal. Effects of timings of administration were investigated using a crossover study. Average serum concentrations in the group administered with the drug before meal reached their peaks at 1 hour after administration with an average level of 2.34 +/- 0.16 micrograms/ml and diminished with a half-life of 1.94 +/- 0.08 hours to 0.29 +/- 0.04 microgram/ml at 8 hours after administration. In the group administered with the drug after meal, average serum concentrations attained their peaks at 4 hours after administration at an average level of 1.93 +/- 0.09 micrograms/ml, and decreased with a half-life of 2.08 +/- 0.19 hours to 0.58 +/- 0.16 microgram/ml at 8 hours. Urinary recovery rates of CPDX in the first 8 hours after administration of CPDX-PR in the before-meal and the after-meal groups averaged 34.4 +/- 6.3% and 38.5 +/- 7.0%, respectively. In a separate experiment, 7 cases were administered with CPDX-PR, 30 minutes after meal, at a dose level of either 3 or 6 mg/kg. Effects of the 2 different dose levels were investigated also using a crossover study. Average serum concentrations at their peaks attained at a 4 hours after administration for the 2 dosage groups (3 and 6 mg/kg) were 1.76 +/- 0.11 and 3.08 +/- 0.41 micrograms/ml, respectively. Average half-life values for the 2 groups were 2.40 +/- 0.14 and 2.25 +/- 0.07 hours, respectively, with average 8 hour values of 0.64 +/- 0.10 and 1.30 +/- 0.21 micrograms/ml, respectively. Urinary recovery rates in the first 8 hours after administration averaged 40.4 +/- 3.2% and 46.3 +/- 6.5%, respectively. From these results, it appeared that the absorption of the drug was affected by the timing of administration (before or after meal), and the presence of ingested foods in the digestive system delayed the absorption. The overall quantity absorbed, however, did not seem to be affected by the timing of administration. These data also showed that serum and urinary concentrations of the drug depended on dose levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Studies on sultamicillin in the field of pediatrics

Pharmacokinetic and clinical studies on sultamicillin (SBTPC) were carried out in the field of pediatrics. 1. Absorption and excretion. A crossover study with a single oral administration of 10 mg/kg of SBTPC in fasting and after meal, and that with 10 mg/kg and 20 mg/kg of SBTPC after meal were carried out in 11 children (5-15 years) and in 6 children (8-15 years), respectively. Serum levels and urinary excretion of sulbactam (SBT) and ampicillin (ABPC) were determined. Mean serum concentrations of ABPC after oral administration of 10 mg/kg of SBTPC with in fasting or after meal, in the former study, peaked at 4.75 +/- 1.97 micrograms/ml in 1 hour and declined with a mean half-life of 0.81 +/- 0.18 hour and the mean serum concentration of ABPC at 6 hours after administration was 0.06 +/- 0.07 micrograms/ml. Mean serum concentration of ABPC study in the latter peaked at 2.95 +/- 0.79 micrograms/ml in 1 hour, and declined with a mean half-life of 1.35 +/- 0.43 hours, and the mean serum concentration of ABPC at 6 hours was 0.22 +/- 0.13 microgram/ml. Mean urinary recovery rates of ABPC in 6 hours after administration were 54.5 +/- 17.6% in the former study, and 63.2 +/- 14.3% in the latter. These results suggested a delay of absorption with meal. Mean serum concentrations of ABPC after oral administration of 10 mg/kg or 20 mg/kg of SBTPC after meal, in the former study, were 3.10 +/- 0.72 micrograms/ml at 1 hour and declined with a half-life of 1.22 +/- 0.32 hours, and those of ABPC were 0.22 +/- 0.12 microgram/ml at 6 hours, and they were 6.46 +/- 1.57 micrograms/ml, 1.48 +/- 0.51 hours and 0.55 +/- 0.40 microgram/ml, respectively in the latter study. Mean urinary recovery rates of ABPC in 6 hours, were 50.4 +/- 10.2% in the former study and 57.7 +/- 11.4%, in the latter. A dose response was observed with time course of mean serum concentrations. Mean serum concentrations of SBT were lower than those of ABPC, and they declined in a similar manner. The mean urinary recovery rate of SBT was similar or lower than that of ABPC. 2. Clinical study SBTPC was used for the treatment of a total of 38 pediatric patients with ages 6 months to 11 years and it's clinical effectiveness, bacteriological efficacy and adverse effects were evaluated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of rokitamycin on young rats with hyperbilirubinemia--determination of unbound and brain bilirubin levels and examination for localized yellow discoloration of brain tissue

The effects of rokitamycin (RKM), a macrolide antibiotic, on young rats with hyperbilirubinemia were investigated. RKM at a dose of 1,000 mg/kg was orally administered to 14-day-old rats with hereditary, non-hemolytic hyperbilirubinemia (homozygous Gunn rats, total plasma bilirubin concentration: about 7 mg/dl). Animals given 10 ml/kg of 0.5% carboxymethyl cellulose (CMC) were used as control. Plasma total bilirubin concentration, plasma unbound bilirubin concentration and cerebellar bilirubin level did not significantly change during 1, 3, 6 and 24 hours after administration of RKM or CMC. There was no significant difference in plasma total bilirubin concentration, plasma unbound bilirubin concentration and cerebellar bilirubin level between RKM-treated and control animals at 1, 3, 6 and 24 hours after the administration. No localized yellow discoloration of the brain tissue (non-cerebellar parts) was noted at 1, 3, 6 and 24 hours after administration of either RKM or CMC.     

Laboratory and clinical studies of rokitamycin in pediatric fields

We have carried out laboratory and clinical studies on rokitamycin (RKM, TMS-19-Q). The results are summarized as follows. Serum and urinary concentrations of RKM were determined in 6 children with ages between 6 and 12 years given single oral doses of 5, 10 and 15 mg/kg. Mean serum concentrations peaked at 30 minutes after administration of 5, 10 and 15 mg/kg, and respective peak values were 0.30 microgram/ml, 0.79 microgram/ml and 1.32 micrograms/ml. Biological half-lives for 5, 10 and 15 mg/kg were 2.0 hours, 1.65 hours and 1.36 hours. The 6-hour urinary recovery ranged from 1.11% to 2.58% after administration of 5 mg/kg, and the mean 6-hour urinary recoveries were 1.35% after administration of 10 mg/kg and 2.28% after administration of 15 mg/kg. Therapeutic responses were recorded as excellent or good in 22 (73.3%) of the children, comprising 6 with tonsillitis, 2 with pharyngitis, 4 with bronchitis, 1 with bronchopneumonia, 1 with Mycoplasma pneumonia, 2 with whooping cough, 5 with streptococcal infections, 5 with Campylobacter enteritis, 3 with impetigo and 1 with SSSS. The microbiological effectiveness of RKM on identified pathogens comprising 4 strains of Staphylococcus aureus, 1 strain of Streptococcus pneumoniae, 6 strains of Streptococcus pyogenes, 4 strains of Haemophilus influenzae and 5 strains of Campylobacter spp. was not so satisfactory as evidenced by a eradication rate of 50.0%. No significant side effect due to the drug was observed in any cases. In conclusion, RKM was found to be efficacious and safe for the treatment of bacterial infections in children.     

Pharmacokinetic studies on oral antibiotics in pediatrics. V. A pharmacokinetic study on cefdinir in pediatrics]

A pharmacokinetic study was performed on cefdinir (CFDN, FK482) 5% fine granules for pediatric use, and pharmacokinetic parameters were calculated. 1. Twenty school children were administered orally a dose level of 3 mg/kg of CFDN fine granules either at 30 minutes before meal (14 children) or 30 minutes after meal (6 children). Plasma concentrations and urinary recovery rates of CFDN were measured. Tmax, Cmax, T 1/2 and urinary recovery rate (0-8 hours) following the administration before meal were 2.00 +/- 0.00 hours, 1.14 +/- 0.11 micrograms/ml, 1.63 +/- 0.14 hours and 23.68 +/- 2.92%, respectively, Tmax, Cmax, T1/2 and urinary recovery rate following the administration after meal were 3.67 +/- 0.33 hours, 0.71 +/- 0.06 micrograms/ml, 2.18 +/- 0.16 hours and 21.76 +/- 2.36%, respectively. Earlier Tmax and higher Cmax were observed when the drug was administered before meal than when administered after meal. There was no statistically significant difference between the 2 groups in urinary recovery rates. However, statistically significant difference was found between the 2 groups when the cross-over technique was used in 6 school children. Nineteen younger children (before meal) and 6 younger children (after meal) were administered with the drug in the same way, and several parameters were measured. Tmax, Cmax, T1/2 and urinary recovery rate following the administration before meal were 2.11 +/- 0.11 hours, 0.98 +/- 0.14 micrograms/ml, 1.71 +/- 0.23 hours and 23.60 +/- 1.72%, respectively, Tmax, Cmax, T1/2 and urinary recovery rate following the administration after meal were 3.33 +/- 0.42 hours, 0.47 +/- 0.14 micrograms/ml, 2.35 +/- 0.27 hours and 12.24 +/- 2.02%, respectively. Earlier Tmax, higher Cmax and higher urinary recovery rate were observed when the drug was administered before meal than when administered after meal. Seven infants (before meal) and 8 infants (after meal) were administered with the drug in the same way, and several parameters were measured. Tmax, Cmax, and T1/2 following the administration before meal were 4.00 +/- 0.62 hours, 0.61 +/- 0.13 micrograms/ml and 3.14 +/- 0.62 hours, respectively, Tmax, Cmax and T 1/2 following the administration after meal were 3.75 +/- 0.25 hours, 0.79 +/- 0.13 micrograms/ml and 2.44 +/- 0.42 hours, respectively. These was no statistically significant difference between the 2 groups. 2. Twenty one school children were administered orally with CFDN fine granules at 30 minutes before meal ata dose level of either 3 mg/kg (14 children) or 6 mg/kg (7 children). Plasma concentrations and urinary recovery rate of CFDN were measured.(ABSTRACT TRUNCATED AT 400 WORDS)     

Basic and clinical studies on clarithromycin in pediatrics

Clarithromycin (TE-031, A-56268) is a new macrolide antibiotic developed by Taisho Pharmaceutical Co., Ltd. Basic and clinical studies in the field of pediatrics were carried out on a granular preparation and 50 mg tablets of TE-031 designed for use in children. The following results were obtained. 1. Concentrations of TE-031 in the serum and its excretion in the urine were investigated in children. Six children were orally administered with a TE-031 granular preparation at 10 mg/kg in a cross-over study 30 minutes before meal and 30 minutes after meal. When the drug was ingested before meal, the mean peak serum concentration occurred 1 hour later and was 5.32 +/- 1.20 micrograms/ml. The mean half-life of TE-031 in the serum was 3.6 +/- 1.0 hours, and drug levels decreased to 1.94 +/- 0.55 micrograms/ml at 6 hours after dosing. In cases of the postprandial administration, the mean peak serum level was 4.21 +/- 1.25 micrograms/ml, occurring 2 hours after ingestion. The mean serum half-life in these cases was 3.5 +/- 1.3 hours, and serum levels decreased to 1.66 +/- 0.47 micrograms/ml at 6 hours after dosing. Mean urinary recovery rates during the initial 6 hours after ingestion were 30.5 +/- 6.4% in the cases of preprandial administration and 34.7 +/- 7.3% with postprandial administration. In addition, 30 minutes before meal, 50 mg tablets of TE-031 were orally administered to 3 children in a dose level equivalent to approximately 10 mg/kg, followed by monitoring of serum and urinary levels. It was found that the mean serum concentration showed a peak value of 4.10 +/- 0.44 micrograms/ml at 2 hours after dosing, the mean serum half-life was 3.5 +/- 0.7 hours, and the mean level fell to 1.90 +/- 0.55 micrograms/ml by 6 hours after dosing. The mean 6-hour urinary recovery rate was 32.7 +/- 12.1%. On the basis of the above results, it has been surmised that, in comparison to conventional macrolide antibiotics. TE-031 is better maintained in the blood at a high concentration and is more efficiently excreted into the urine. In addition, the data show that the bioavailability of TE-031 is slightly superior when the drug is administered on an empty stomach compared with after a meal. And finally, it was found that the granular and 50 mg tablet preparations of TE-031 are almost equivalent in terms of the absorption and the excretion of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical study of rokitamycin dry syrup in pediatrics

A total of 22 patients with acute pediatric infections was treated with rokitamycin (TMS-19-Q, RKM) dry syrup, a new macrolide antibiotic developed by Toyo Jozo Co., Ltd., Ohhito, Japan, to investigate its clinical efficacy. 1. A girl of an age 4 years 2 months (weighing 16.5 kg) was administered orally 10 mg/kg of RKM, and a boy of an age 8 years 7 months (weighing 24.5 kg), 15 mg/kg, and blood concentrations of RKM in these subjects were measured to investigate its absorption and excretion. Blood concentrations of the drug reached a peak of 0.84 microgram/ml in an hour after the administration in the girl, 0.72 microgram/ml in 30 minutes in the boy, with T1/2 of 0.86 and 1.82 hours, respectively. Their 6-hour cumulative urinary recovery rates were 2.79 and 2.13%, respectively. 2. A total of 20 patients was treated with RKM dry syrup. These patients included 3 with acute pharyngitis, one with acute tonsillitis, 4 with hemolytic streptococcal infections, 7 with acute bronchitis, 2 with pneumonia, another 2 with pertussis, and one with Campylobacter enteritis. The treatment was effective in 18 of them with a clinical efficacy of 90.0%. 3. Bacteriological responses to RKM dry syrup were as follows: eradication of pathogens in 5, pathogens decreased in 3, and no changes were observed in 3 of 12 patients from whom pathogens had been isolated prior to the treatment, thus the eradication rate was 45.5% with the exception of 1 patient whose bacteriological response was unknown.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bacteriological, pharmacokinetic and clinical studies on a rokitamycin dry syrup in the pediatric field

Bacteriological, pharmacokinetic and clinical studies were done on the effect of rokitamycin (RKM, TMS-19-Q) in the field of pediatrics. The results are summarized below. 1. Antibacterial activities Antibacterial activities of RKM against Staphylococcus aureus (including 50 methicillin-sensitive and 50 methicillin-resistant strains), 18 strains of Haemophilus influenzae and 50 strains of Campylobacter jejuni were studied comparatively with activities of josamycin (JM), midecamycin (MDM), erythromycin (EM) and cefaclor (CCL) or ampicillin. Minimum inhibitory concentrations (MICs) of the 5 antibiotics against methicillin-sensitive S. aureus showed a wide variation but RKM was somewhat superior among them. MIC80 of those antibiotics tested against methicillin-sensitive S. aureus were as follows; RKM 1.56, JM 12.5, MDM 12.5, EM 6.25, and CCL 3.13 micrograms/ml. Among methicillin-resistant S. aureus (MRSA), ratios of strains highly resistant to these antibiotics (MIC greater than or equal to 100 micrograms/ml) to total number of strains tested were: 18% to RKM, and 26%, 34% and 48% to JM, MDM and EM, respectively, again showing the superiority of RKM and the proliferation of resistant organisms to EM. MICs of RKM against H. influenzae were distributed in a range between 0.78 and 12.5 micrograms/ml, which were similar to MIC range of CCL, and approximately twice as high as that of EM, but 4 folds lower than those of JM and MDM. Against C. jejuni, the MIC range of RKM was quite broad, 0.10-12.5 micrograms/ml, with a peak value of 0.20 micrograms/ml. The cumulative number of strains vs. MIC curve was similar to that of EM, and RKM was approximately 4 to 8 folds more effective than the other 3 antibiotics. 2. Absorption and excretion The absorption and the excretion of RKM were studied with its dry syrup preparations. Dose levels examined were 5 mg/kg in 2 cases, 10 mg/kg in 7 cases, 15 mg/kg in 2 cases and 20 mg/kg in 1 case. Peak concentrations of RKM in blood were not dose-dependent and were 0.16-0.23, 0.29-0.91, 0.35-0.46 microgram/ml and 0.53 microgram/ml, respectively, for the 4 dose levels. Most of drug levels dropped below the detection limit in 4 hours after the administration when dose levels up to 10 mg/kg were used, and when dose levels were at or above 15 mg/kg, 0.07-0.09 microgram/ml of RKM was detected in blood at 6 hours after the administration. Urinary recovery rates in 6 hours were between 0.19 and 3.31%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic studies on oral antibiotics in pediatrics. I. A pharmacokinetic study on cefixime in pediatrics

A pharmacokinetic study on cefixime (CFIX) 5% granules for pediatric use was performed, and pharmacokinetic parameter were calculated. 1. Six school children were administered orally with CFIX granules at a dose level of 3 mg/kg either at 30 minutes before meal or at 30 minutes after meal on a crossover design, and serum concentrations and urinary excretion rates of CFIX were determined. Tmax, Cmax, T 1/2 and urinary excretion rate (0-12 hours) following the administration before meal were 3.33 +/- 0.42 hours, 1.03 +/- 0.17 micrograms/ml, 2.31 +/- 0.26 hours and 15.3 +/- 2.2%, respectively, Tmax, Cmax, T 1/2 and urinary excretion rate following the the administration after meal were 4.00 +/- 0.52 hours, 0.90 +/- 0.09 micrograms/ml, 3.11 +/- 0.21 hours and 11.3 +/- 1.6%, respectively. Earlier Tmax, higher Cmax and higher urinary excretion rate were observed when the drug was administered before meal than when administered after meal. These differences between the 2 groups were not statistically significant. 2. Five school children were administered orally with CFIX granules at 30 minutes after meal at a dose level of either 3 mg/kg or 6 mg/kg on a crossover design, and serum concentrations and urinary excretion rates of CFIX were determined. Cmax and AUC at a dose level of 3 mg/kg were 1.01 +/- 0.26 mg/ml and 5.86 +/- 1.13 micrograms.hr/ml, respectively, and Cmax and AUC at a dose level of 6 mg/kg were 1.76 +/- 0.29 micrograms/ml, 12.54 +/- 1.77 micrograms.hr/ml, respectively. A dose response relationship was thus observed. Seven infants (3 mg/kg) and 3 infants (6 mg/kg) were administered orally with CFIX granules at 30 minutes after meal. Cmax and AUC at a dose level of 3 mg/kg were 2.45 +/- 0.26 micrograms/ml, 33.50 +/- 7.62 micrograms.hr/ml, respectively, and Cmax and AUC at a dose level of 6 mg/kg were 4.42 +/- 0.98 micrograms/ml, 66.85 +/- 25.19 micrograms.hr/ml, respectively. A dose response was observed. 3. Eleven school children, 5 younger children and 7 infants were administered orally with CFIX granules at a dose level of 3 mg/kg at 30 minutes after meal, and serum concentrations and urinary excretion rates of CFIX were determined. Tmax in school children, younger children and infants were 3.82 +/- 0.33 hours, 5.20 +/- 0.49 hours and 5.43 +/- 0.37 hours, respectively. Earlier Tmax's were observed in school children than in other children. Cmax in school children, younger children and infants were 0.95 +/- 0.12 micrograms/ml, 0.56 +/- 0.06 micrograms/ml and 2.45 +/- 0.26 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetics of clarithromycin granule and tablet in children

It has been known that clarithromycin (TE-031, A-56268), a new macrolide antibiotic (ML), achieves higher concentrations in blood, is better excreted into urine and is better distributed into various tissues than conventional MLs. We investigated the pharmacokinetics of TE-031 in children upon oral administration of the drug in the following method. TE-031 granular preparation with a potency of 100 mg/g was given to 6 boys (5 years 4 months-14 years 0 month) with dose levels of 5 mg/kg and 10 mg/kg for each 3 boys. A tablet preparation with each tablet containing 50 mg of TE-031 was administered to 4 boys and 2 girls (8 years 5 months-11 years 6 months) with dose level of 2 tablets (i.e., 100 mg) and 3 tablets (i.e., 150 mg) for each 3 children. All administrations were done at 30 minutes before meal. Then, to conduct a cross-over test, the granule preparation was given orally to the 3 children mentioned above who was given 2 tablets and the 1 of 3 cases that were given 3 tablets at the same dose levels (100 mg and 150 mg) respectively. A bioassay was used to determine concentrations in blood of active antibiotic compounds and an high performance liquid chromatography (HPLC) was used to determine unchanged TE-031 and its main metabolite, M-5. Urinary concentrations of active antibiotic compounds were also determined by the bioassay and the HPLC was used to determine concentrations and proportions of unchanged TE-031 and its metabolites, M-1, M-4, M-5, M-6 and M-7 to figure out the urinary recovery rate in the first 6 hours. The results of these experiments are summarized as follows. 1. As was mentioned above, TE-031 was administered orally to 2 groups of children at dose levels of 5 mg/kg and 10 mg/kg, respectively. Mean serum levels of total active antibiotic compounds reached their maximum in 1 and 2 hours for the 5 mg/kg and the 10 mg/kg dosage groups, respectively, at 1.28 and 3.62 micrograms/ml, respectively. Mean half lives of serum concentrations in the 2 groups were quite similar, with values of at 2.1 and 2.0 hours, respectively. Mean serum concentrations of unchanged TE-031 determined by the HPLC method reached their peaks in 1 hour after administration in either of the 5 and 10 mg/kg dosage groups at peak levels of 0.65 micrograms/ml and 2.67 micrograms/ml, respectively. Thus, dose-response relationships were observed with TE-031 and M-5.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical evaluation of cefteram pivoxil fine granules in pediatric infections

Cefteram pivoxil (CFTM-PI), in fine granules, was studied in pediatric infections and the results obtained are summarized below. It is concluded that CFTM-PI fine granule is an effective drug for the treatment of pediatric infections. 1. The pharmacokinetics of CFTM-PI fine granules was studied in 7 patients (5 males, 2 females) whose ages ranged from 9 to 15 years. (1) In 2 patients, administered with the drug at a dose of 3 mg/kg in the fasting state, serum peak concentrations of CFTM at 2 hours after administration were 0.66 and 0.53 micrograms/ml, and T 1/2 were 1.40 and 1.32 hours, respectively. Urinary recovery rates in the first 8 hours were relatively low at 5.8 and 10.8%, respectively. (2) In 1 patient, the drug administered at a dose of 6 mg/kg in the fasting state, serum peak concentration of CFTM at 2 hours after administration was 3.0 micrograms/ml, T 1/2 was 2.16 hours, and urinary recovery rate in the first 8 hours was 13.8%. In another 2 patients, CFTM-PI administered at a dose of 6 mg/kg after meal, serum peak concentrations of CFTM at 4 hours after administration were 5.8 and 2.5 micrograms/ml, T 1/2 of the latter was 1.93 hours, and urinary recovery rates in the first 8 hours were 27.0 and 14.4%, respectively. (3) In yet another 2 patients, CFTM-PI tablets was administered at a dose level of 150 mg after meal. Serum peak concentrations of CFTM were 1.7 and 1.6 micrograms/ml at 2 hours and 4 hours after administration, respectively, T 1/2 of the former was 1.38 hours, and urinary recovery rates were 24.1 and 15.5%, respectively. 2. Clinical results CFTM-PI as fine granules was administered to 18 patients, and the following results were obtained. (1) 12 cases (6 males, 6 females) with their ages ranged from 3 months to 12 years were administered with the drug at a dose of 10 mg/kg/day, divided into 3 equal portions. Clinical efficacies were fair in 1 case with bronchopneumonia, good in 3 cases with bronchitis and in 4 cases with tonsillitis/pharyngitis, excellent in 1 and good in another with scarlet fever, and good in 1 and poor in another with urinary tract infection (UTI) (2) Six cases (4 males, 2 females) with their ages were 6 and 7 years were administered with CFTM-PI at a dose of 20 mg/kg/day divided into 3 equal portions. Clinical efficacies were good in 1 case with bronchopneumonia, 2 cases with bronchitis and 3 cases with tonsillitis/pharyngitis.     

Pharmacokinetic, bacteriological and clinical studies in the pediatric field on clarithromycin

Pharmacokinetic, bacteriological and clinical studies were carried out on clarithromycin (TE-031, A-56268) in the pediatric field and following results were obtained. 1. Peak concentrations of TE-031 in the serum occurred at 1-2 hours after administration of 10 mg/kg in granular form and at 2 hours after administration of 20 mg/kg in granular form. Half-lives of the drug in serum were 2.5-3.3 hours in cases of 10 mg/kg dosage and 5.5 hour in case of 20 mg/kg dosage. TE-031 tablets were administered in a dosage between 1.7 and 5.0 mg/kg and peak concentrations in the serum occurred at 0.5-2 hours. Half-lives were 2.0-4.3 hours. 2. Urinary recovery rates obtained upon administration of TE-031 granule during the first 6 hours after administration were 20.3-62.9%, while they were 11.6-42.4% with TE-031 tablets. 3. Antibacterial activity of TE-031 against Campylobacter jejuni was equal to that of erythromycin and slightly superior to those of josamycin, midecamycin acetate and rokitamycin. 4. Bacteriological efficacy rate of TE-031 on 8 species of bacteria isolated from various samples was 88.4% and clinical efficacy rate on 66 cases (upper/lower respiratory tract infections, mycoplasmal pneumonia, Campylobacter enteritis, et al.) was 100%. 5. TE-031 was administered in dosages of 6.8-42.3 mg/kg/day (mostly 20-30 mg/kg/day) 3 times a day and lengths of administration ranged from 4 to 15 days. 6. Side effects due to TE-031 were observed in 1 case each of transient symptom and abnormal clinical laboratory test value. According to the above results, TE-031 was recognized as a useful antibiotic for the treatment of infections in the pediatric field.     

Clinical study on 9,3"-diacetylmidecamycin in the field of pediatrics (author's transl)

We have studied clinically on 9,3"-diacetylmidecamycin (MOM), a new macrolide antibiotic derived from midecamycin. The following results were obtained. 1) Serum concentration. To the the same child weighing 15 kg and aged 4 years, the MOM dry syrup was administered orally at single doses of 150 mg (10 mg/kg) and 300 mg (20 mg/kg) and then the MDM fine granules at a single dose of 300 mg (20 mg/kg). At dosages of 10 mg/kg and 20 mg/kg of MOM dry syrup and 20 mg/kg of MDM fine granules, the serum concentrations were 0.5 microgram/ml, 0.8 microgram/ml and not detectable (N.D.) respectively, at 45 minutes after administration; 0.4, 0.6 and N.D. at 1 hour; 0.12; 0.2 and N.D, at 2 hours; N.D., less than 0.1, N.D. at 4 hours; N.D. in all the cases at 6 hours. 2) Clinical results. MOM dry syrup was administered to 25 children. The efficacy rate was 68.75% except for 1 dropout case and the elimination rate of 11 isolated strains of group A Streptococcus was 9.09% in 16 cases of scarlet fever and 1 of acute pharyngitis caused by group A Streptococcus. With 6 cases of pertussis were eradicated. The clinical response to 1 with acute bronchitis and 1 with Mycoplasma pneumonia were good and poor respectively. 3) Side effect. No clinical side effect and abnormal laboratory findings were observed in any of the 25 cases administered MOM dry syrup.     

Pharmacokinetics and clinical effects of cefdinir 10% fine granules in pediatrics]

Cefdinir (CFDN), a newly developed oral cephalosporin in a 10% fine granular form, was administered to 8 children and concentrations of the drug in plasma and urine and urinary recovery rates of the drug were determined. The subjects were divided into 2 groups of 4 children each; one group received 3 mg/kg of CFDN at 1 hour before meal (in the fasting state), and the other, at 30 minutes after meal. To study clinical and bacteriological effects of this drug, a mean dose of 4.8 mg/kg t.i.d. was administered for 8 days on the average to 9 children with various infections; tonsillitis (3 cases), acute bronchitis (1), pneumonia (1), acute purulent otitis media (1), urinary tract infection (2), and impetigo (1). MICs were determined for 6 drugs including CFDN, cefaclor, cefixime (CFIX), methicillin, cloxacillin, amoxicillin (AMPC) against 4 strains freshly isolated from children receiving CFDN. An inoculum size of 10(6) cfu/ml was used in the MIC-determinations. Adverse reactions and abnormal laboratory findings attributable to this drug were also examined in these children. The results obtained are summarized as follows. 1. Mean plasma peak levels of CFDN were observed at 2 hours after administration in the before-meal group and 4 or 5 hours after administration in the after-meal group mean peak values of 0.88 and 0.50 micrograms/ml, respectively. Mean half-lives were 1.61 hours in the before-meal group and 2.54 hours in the after-meal group, and mean AUCs were 4.24 in the former and 3.59 micrograms.hr/ml in the latter. 2. Mean urinary peak concentrations of CFDN were observed during 2-4 hours after dosing in the before-meal group and during 6-8 hours in the after-meal group with values of 93.3 and 44.8 micrograms/ml, respectively, in cases for which plasma concentrations of drugs were determined. Mean urinary recovery rates during the first 8 hours after administration in the before- and after-meal groups were 16.6 and 13.4%, respectively. 3. Good clinical effects were obtained with an efficacy rate of 100% in 9 patients with 6 diseases due to bacterial infections. 4. Good bacteriological effects were also obtained against 2 strains of Streptococcus pyogenes, 2 strains of Escherichia coli and 1 strain of Haemophilus influenzae with an eradication rate of 100%. In 3 cases of these and another case (normal flora), strains present before the study were replaced by other strains.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical and pharmacokinetic evaluation of a +rokitamycin dry syrup in children

Twenty five children were treated with rokitamycin (RKM) and its clinical efficacy and side effects were evaluated. Ages of the patients ranged from 13 days to 10 years. Doses of RKM ranged 17.1-39.3 mg/kg/day for 2.3 to 17.7 days. Twenty four patients including 8 Mycoplasma pneumonia, 5 bronchopneumonia, 6 bronchitis, 2 streptococcosis, 1 otitis media, 1 tonsillitis and 1 Chlamydia conjunctivitis were evaluated for clinical efficacy. Results were excellent in 7, good in 12, fair in 4, and poor in 1 patient. One patient was excluded from the evaluation, because the patient was treated with erythromycin before entering this study. Out of the 25 patients, 3 cases showed eosinophilia, 2 cases showed elevated GOT and GPT but no adverse clinical signs due to RKM were observed. The pharmacokinetics of RKM was studied in 5 patients whose ages ranged from 8 to 12 years. Plasma peak concentrations of RKM in 2 patients were 0.14 and 0.16 micrograms/ml at 30 minutes after doses of 5 mg/kg. Peak concentrations in 3 patients ranged from 0.32 to 1.02 micrograms/ml after doses of 10 mg/kg. Portions of the drug excreted into urine within 6 hours were 0.49 and 1.03% in 2 patients each of whom was given doses of 5 mg/kg, and ranged from 1.16 to 1.30% in 3 patients, each given 10 mg/kg. Metabolic products in urine within 4 hours after doses of 5 to 10 mg/kg were studied in 4 patients. Leucomycin A7 and leucomycin V accounted for almost 90% of all the related compounds excreted.     

Pharmacokinetics of a sustained-release theophylline formulation.

1 Plasma theophylline concentrations following administration of sustained-release (SR) theophylline tablets were determined in ten healthy volunteers using a dose of 190 mg or 380 mg 12 hourly. 2 The plasma theophylline levels during the first 12 h period confirmed the sustained-release formulation characteristics, with the plasma drug concentrations reaching a plateau for the last 6 hours. 3 During the fifth 12 h dosing period the mean maximum and minimum plasma theophylline concentrations were 7.25 and 4.30 microgram/ml after 190 mg SR theophylline 12 hourly (n = 6) and 12.96 and 7.36 microgram/ml after 380 mg 12 hourly (n = 5), although there was marked between-subject variation in plasma theophylline concentrations. 4 One subject withdrew from the study due to side effects, which were more common when the higher dose of SR theophylline was given.     

The study of flomoxef in the pediatric field

Flomoxef (FMOX; 6315-S), a new synthetic oxacephem antibiotic, was studied in the pediatric field and pharmacokinetic and clinical results obtained were summarized below. 1. The activity of FMOX against Staphylococcus aureus isolated from clinical patients, including latamoxef resistant strains was very high and MIC was approximately less than or equal to 0.39 microgram/ml. This MIC value was lower than other cephem antibiotics such as cefotaxime, cefotiam, cefmetazole, cefamandole. The distribution of MIC's of FMOX against Escherichia coli and Salmonella spp. ranged from 0.05 to 0.78 microgram/ml and from 0.05 to 0.39 microgram/ml, respectively. 2. Serum concentrations of FMOX after dosages of 20 mg/kg and 40 mg/kg with 1 hour intravenous drip infusion were 21.5-27.5 micrograms/ml, 6.00-7.81 micrograms/ml, 0.37-0.59 micrograms/ml at 1, 2, 5 hours after administration, respectively, and T1/2(beta) were 0.61-0.83 hour. Serum concentrations after one shot intravenous injection of 20 mg/kg FMOX were 56.7-90.2 and 0.20-0.26 micrograms/ml at 3-10 minutes and 6 hours after administration, respectively, T1/2(beta) was 1.22 hours and urinary excretion rate was 66.7-69.8% in 6 hours. 3. FMOX was administered to 32 cases (upper and lower respiratory tract infection, and purulent infections) at 3-4 times daily for 4-13 days. In these cases the daily dosage amounted to 41-119 mg/kg. Clinical effectiveness was 97% overall including resistance cases upon other cephem antibiotic treatment. All bacterial species identified including Branhamella catarrhalis, Streptococcus pyogenes, S. aureus, Streptococcus agalactiae, and Haemophilus influenzae were eradicated upon the treatment with FMOX. 4. Only 3 cases of soft stool, 1 case of elevated GOT and GPT, and 1 case of elevated GPT were observed, and all of these adverse reactions were normalized after the completion of treatment.     

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium in neonates and premature infants

Imipenem/cilastatin sodium (IPM/CS) was administered in a dose of 10 mg/10 mg/kg or 20 mg/20 mg/kg by a 1-hour intravenous drip infusion to 19 mature and premature neonates with ages from 1 to 12 days with various bacterial infections, and plasma concentrations and urinary recovery rates in these subjects were measured. Because of the small number of patients recruited, neonates were not divided into mature and premature groups, but into 3 groups based on their day-ages: 0-3 days, 4-7 days and 8 days or older. A clinical evaluation of IPM/CS was carried out in 10 male and 3 female neonates with ages 0-28 days. These patients included 6 with pneumonia, 4 with urinary tract infection and 1 each with septicemia, suspected septicemia and maxillary sinusitis. 1. Plasma concentrations and urinary recovery rates (1) The 1-hour intravenous drip infusion at 10 mg/10 mg/kg of IPM/CS IPM: Its peak plasma concentrations were obtained at the end of drip infusion of the test drug in all 3 groups, their values ranged from 18.18 to 19.90 micrograms/ml with no statistically significant variations. The plasma concentrations rapidly decreased to 0.32-0.98 microgram/ml at 8 hours after administration of IPM/CS. The half-lives tended to be shorter in older neonates, with mean half-lives being 1.87, 1.55 and 1.40 hours, respectively. CS: Its peak plasma concentrations were obtained for all 3 groups at the end of drip infusion and were ranging from 28.23 to 30.00 micrograms/ml with no significant variations. Plasma concentrations in the 0-3 day-age group and the 4-7 day-age group slowly decreased to 6.30 micrograms/ml and 4.58 micrograms/ml at 8 hours after administration of IPM/CS, respectively. Half-lives were 4.10 hours and 3.08 hours, respectively. On the other hand, those of the 8-day or older group rapidly decreased to below the detection limit in 8 hours after administration with a half-life of 1.6 hours. (2) The 1-hour intravenous drip infusion at 20 mg/20 mg/kg of IPM/CS IPM: Peak plasma concentrations were obtained in all 3 groups at the end of drip infusion and were ranging from 31.1 to 38.24 micrograms/ml. Plasma concentrations rapidly decreased, and were 0.95-2.08 micrograms/ml at 8 hours after administration with half-lives of 1.5-1.88 hours. CS: Peak plasma concentrations were obtained in all 3 groups at the end of drip infusion and were ranging from 47.0 to 55.82 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

Basic studies of cefotiam (author's transl)

The basic studies of cefotiam (CTM) were performed, and the following results were obtained. 1. One shot intravenous injection of 40 mg/kg of CTM (1) Serum levels: The mean levels of CTM in 3 children were 133.9 micrograms/ml after 15 minutes, 71.5 micrograms/ml after 30 minutes 32.6 micrograms/ml after 1 hour, 9.2 micrograms/ml after 2 hours, 2.5 micrograms/ml after 4 hours, 0.9 microgram/ml after 6 hours. The serum half life of CTM was approximately 1.2 hours on beta-phase. (2) Urinary excretion: The mean urinary excretions were 39.4% over 3 hours, 44.7% over 4 hours, 45.7% over 6 hours. 2. 1 hour-drip infusion of 40 mg/kg of CTM (1) Serum levels: The mean serum levels of CTM in 4 children were 140.1 micrograms/ml at immediately after drip infusion was completed, 10.6 micrograms/ml after 1 hour, 3.8 micrograms/ml after 2 hours, 1.4 micrograms/ml after 3 hours, 0.5 microgram/ml after 5 hours. The serum half life of CTM was approximately 1.0 hour on beta-phase. (2) Urinary excretions: The mean urinary excretions were 42.9% over 2 hours, 48.0% over 4 hours, 48.7% over 6 hours. 3. Bioactive metabolite in serum and urine: No bioactive metabolites were observed in either serum or urine after administration of 40 mg/kg of CTM.