title: Population pharmacokinetics of tebipenem pivoxil (ME1211), a novel oral carbapenem antibiotic, in pediatric patients with otolaryngological infection or pneumonia.
abstract: Tebipenem pivoxil (TBPM-PI, ME1211) has been under development as the world's first oral carbapenem for treatment of otolaryngological/respiratory infections caused by drug-resistant S. pneumoniae in pediatric patients. In order to treat these infections effectively, it is important to design optimal dosing regimens based on the pharmacokinetics/pharmacodynamics (PK/PD) relationships, which can be characterized by clarifying the pharmacokinetics of tebipenem (TBPM) in the pediatric population. We therefore performed an population pharmacokinetic analysis using plasma TBPM concentrations obtained from pediatric patients with otolaryngological infection or bacterial pneumonia (0.5-16 years old; n=217, 395 points), after repeated oral administration of TBPM-PI at a dose of 4 or 6 mg/kg b.i.d. A one-compartment model with first-order absorption was adopted. In analysis, weight-normalized creatinine clearance (Ccr) and age were the most significant covariates that respectively explained inter-subject variability in weight-normalized apparent clearance (CL/F) and volume of distribution (Vd/F) of TBPM. The CL/F of TBPM increased with Ccr, and the Vd/F decreased with age. Based on the results of the present analysis, validity of the presently recommended dosage regimen of TBPM-PI in pediatric patients is discussed.
authors.affiliation: Applied Pharmacology Research Labs., Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Kanagawa, Japan. nobuo_sato@meiji.co.jp
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sato
authors.forename: Koji
authors.initials: K
authors.lastname: Kijima
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Koresawa
authors.forename: Nayu
authors.initials: N
authors.lastname: Mitomi
authors.forename: Jun
authors.initials: J
authors.lastname: Morita
authors.forename: Hisashi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibasaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Kurosawa
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Totsuka
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010038:Otorhinolaryngologic Diseases / Q000188:drug therapy* / Q000378:metabolism*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000378:metabolism*; D011153:Population
chemical_list: D015780:Carbapenems; C500135:tebipenem