[Pharmacokinetic and clinical studies with L-627 (biapenem) in the pediatric field. Pediatric study group of L-627].
To conduct pharmacokinetic and clinical studies on newly developed L-627 (biapenem) against various infections in pediatrics, a study group was organized and a joint research by 15 institutions and their related hospitals was undertaken. Informed consents of subjects were obtained prior to the study. The obtained results are as follows. 1. Plasma concentrations and urinary excretion Pharmacokinetics of L-627 in children was studied in 29 subjects using 30 minutes intravenous drip infusion of 6 mg/kg and 12 mg/kg. Maximum plasma levels of L-627 was observed at the completion of drip infusion and were 25.1 micrograms/ml with administration of 6 mg/kg and 39.2 micrograms/ml with administration of 12 mg/kg on average. Dose dependency was noted in Cmax and AUC with these doses. Maximum blood levels in all of the 5 participated sucklings under the age of one year were similar to the average. As for urinary excretion, L-627 was excreted 66.0% with administration of 5 mg/kg and 62.3% with 12 mg/kg. 2. Cerebrospinal fluid concentrations Cerebrospinal fluid concentrations ranged from 0.76 to 8.54 micrograms/ml in 30-240 minutes after the completion of drip infusion with dose of 20-40 mg/kg in 9 subjects with purulent meningitis, when they were measured within 3 days after the initiation of the treatment with L-627. 3. Clinical results Thirty-three cases of exclusion and drop-out were deducted from a total of 330 cases, hence 297 cases were evaluated as the subjects in the study for analysis of clinical effects. As for clinical effects in group A where pathogenic bacteria were detected, 166 out of 173 were rated as effective or above, hence the efficacy rate of 96.0% was obtained. In group B where pathogenic bacteria were not detected, 114 out of 124 cases were rated as effective or above, thus the efficacy rate was 91.9%, which is similar to that of the group A. The overall efficacy rate was 94.3% in the entire 297 cases. The rates of "excellent" responses out of the cases rated as effective or above were 62.7% (104/166) in the group A and 55.3% (63/114) in the group B, thus the rate was markedly high in the former group. Efficacy rate for each pathogenic strain was also high, and that in subjects infected by a single pathogenic strain was 96.7% (145/150) and that in subjects infected by two or more pathogenic strains was 91.3% (21/23).(ABSTRACT TRUNCATED AT 400 WORDS)
Fujii
R
R
Department of Pediatrics, School of Medicine, Teikyo University.
Fujita
K
K
Yoshikawa
M
M
Murono
K
K
Maruyama
S
S
Sakata
H
H
Inyaku
F
F
Takahashi
S
S
Saino
T
T
Chiba
S
S
D000367:Age Factors; D001419:Bacteria / Q000302:isolation & purification; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D012737:Sex Factors; D013845:Thienamycins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D013845:Thienamycins; C065257:biapenem