[Comprehensive evaluation of pharmacokinetic and clinical studies on tazobactam/piperacillin in pediatric field].
To evaluate the pharmacokinetic and clinical effects of the newly developed combination antibiotic tazobactam/piperacillin (TAZ/PIPC, YP-14) on various infections in pediatric field, a study group was organized, and a joint research by 17 institutions and their related hospitals was conducted. Informed consents of subjects were obtained prior to the study. The results obtained in this study are as follows: 1. Blood concentration and urinary excretion Pharmacokinetics of TAZ/PIPC was studied in children at doses of 25 and 50 mg/kg through intravenous injection or intravenous drip infusion. With intravenous injection, maximum blood concentrations (Cmax's) of TAZ and PIPC were achieved 5 minutes after the administration. Cmax's of TAZ were 26.9 micrograms/ml with 25 mg/kg and 45.1 micrograms/ml with 50 mg/kg, and those of PIPC were 131.0 and 199.6 micrograms/ml, respectively. Values of the total area under the blood concentration curve (AUC's) of TAZ were 14.2 micrograms.hr/ml with 25 mg/kg and 26.1 micrograms.hr/ml with 50 mg/kg, and those of PIPC were 64.0 and 112.8 micrograms.hr/ml, respectively; thus dose dependency was observed with both TAZ and PIPC. The Cmax's of desethyl piperacillin (DEt-PIPC), the active metabolite of PIPC, achieved at 60 minutes after administration, were 1.2 and 2.0 micrograms/ml, respectively. The AUC's of DEt-PIPC were 2.6 and 4.2 micrograms.hr/ml, respectively. The half-lives (T 1/2's) of TAZ were 0.60 and 0.54 hour, respectively, and those of PIPC were 0.62 and 0.65 hour, respectively. In the first 6 hours after the initiation of administration, the cumulative recovery rates of TAZ in the urine were 46.7 and 56.0% respectively, those of PIPC were 46.1 and 57.2%, respectively, and those of DEt-PIPC were 5.9 and 3.0%, respectively. With intravenous drip infusion, the Cmax's of both TAZ and PIPC were achieved at the completion of drip; the Cmax's of TAZ were 12.1 micrograms/ml with 25 mg/kg and 28.9 micrograms/ml with 50 mg/kg, and those of PIPC were 54.6 and 137.9 micrograms/ml, respectively. The AUC's of TAZ were 11.6 micrograms.hr/ml with 25 mg/kg and 25.6 micrograms.hr/ml with 50 mg/kg, and those of PIPC were 49.0 and 117.2 micrograms.hr/ml, respectively; thus dose dependency was observed with both TAZ and PIPC. Cmax's of DEt-PIPC, achieved at 60 minutes after completion of drip, were 0.9 and 1.7 micrograms/ml, respectively. The AUC's of DEt-PIPC were 2.0 and 3.8 micrograms.hr/ml, respectively. The half-lives (T 1/2's) of TAZ were 0.59 and 0.62 hour, respectively, and those of PIPC were 0.58 and 0.57 hour, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Fujii
R
R
Department of Pediatrics, School of Medicine, Teikyo University.
Okuno
A
A
Fujita
K
K
Yoshikawa
M
M
Inyaku
F
F
Takimoto
M
M
Saijo
M
M
Wagatsuma
S
S
Fukushima
N
N
Ishikawa
A
A
D000293:Adolescent; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D002675:Child, Preschool; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D010878:Piperacillin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000078142:Tazobactam
D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin