[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)
Motohiro
T
T
Department of Pediatrics, School of Medicine, Kurume University.
Yoshinaga
Y
Y
Sasaki
H
H
Oda
K
K
Aramaki
M
M
Kawakami
A
A
Tanaka
K
K
Koga
T
T
Shimada
Y
Y
Sakata
Y
Y
D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin; D004304:Dosage Forms; D004917:Erythromycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D013607:Tablets
D004304:Dosage Forms; D013607:Tablets; D004917:Erythromycin; D017291:Clarithromycin