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.

New antibiotics and antimicrobial combination therapy for the treatment of gram-negative bacterial infections

“…'Tebipenem/pivoxil' is a novel oral carbapenem developed for the treatment of upper respiratory tract infections, and its spectrum is mainly orientated on gram-positives, K. pneumonia, and E. coli [73]. Phase 2 clinical studies are ongoing in Japan.…”

New perspectives on antibacterial drug research

“…It shows potent activity against pathogens causing UTI and respiratory tract infections. This oral carbapenem may be a potential drug for treatment of persistent otitis media, upper respiratory infection and bacterial pneumonia in pediatric patients [22,23]. ME1036 is carbapenem drug with strong antibacterial activity against penicillin-resistant S. pneumoniae, E. faecalis, Haemophilus influenzae and Enterobacteriaceae strains but is not active against P. aeruginosa isolates [12,15,24].…”

New treatment options against gram-negative organisms

“…While tebipenem is inactive against MBL-producing pathogens and MRSA, good activity against penicillin-susceptible and penicillin-resistant S. pneumoniae, S. pyogenes, H. influenzae, K. pneumoniae, M. catarrhalis and E. coli has been reported. It is likely to become a specific antibiotic for the treatment of persistent otitis media, upper respiratory infection and bacterial pneumonia in pediatric patients [50]. Phase II clinical studies are being conducted in Japan.…”