title: [Dosing regimen rationalization of biapenem in pediatric patients: use of Monte Carlo simulation].
abstract: Biapenem has been used in pediatric patients as well as adult patients; however, little information is available on dosing regimens for pediatric patients. This study examined biapenem pharmacokinetics in pediatric population and performed pharmacokinetic-pharmacodynamic analysis. Biapenem plasma concentrations from 10 pediatric patients were pharmacokinetically analyzed. A multi-regression analysis showed the pharmacokinetic parameters were affected by body weight and creatinine clearance of the patients. Using the pharmacokinetic parameters, a Monte Carlo simulation predicted the probabilities of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration for the bacterium). In the case of about 20 kg, biapenem regimens of 5 mg/kg b.i.d. and 10 mg/kg b.i.d. provided sufficient target attainment probabilities against Streptococcus pneumoniae and Pseudomonas aeruginosa isolates, respectively. Our results should provide a PK-PD-based guidance for rationalizing biapenem regimen according to the body weight and renal function of a pediatric patient and the specific bacterium suspected.
authors.affiliation: Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kameda
authors.forename: Mizuka
authors.initials: M
authors.lastname: Miki
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000293:Adolescent; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009010:Monte Carlo Method; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012044:Regression Analysis; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D013845:Thienamycins; D003404:Creatinine; C065257:biapenem