An open clinical study of tebipenem pivoxil in children with acute otitis media and acute upper respiratory tract infection (phase II)

We conducted an open clinical study of an oral carbapenem, tebipenem pivoxil (TBPM-PI), in pediatric patients with acute otitis media and acute upper respiratory tract infection to assess efficacy, safety, and drug compliance. We also assessed dosage and administration at 4 mg/kg bid and 6 mg/kg bid set based on confirmatory study results for dosage and administration in adult patients. 1. Clinical effect: Response at the end of administration or at discontinuation was 100% (12/12) in the 4 mg/kg bid group and 100% (10/ 10) in the 6 mg/kg bid group. 2. Bacteriological effect: Bacteriological effectiveness was shown for all 7 strains of causative microorganisms isolated-3 strains in the 4 mg/ kg bid group and 4 strains in the 6 mg/kg bid group - at the end of administration or at discontinuation. 3. Safety: The incidence of adverse drug reaction (subjective symptoms and objective findings) were 16.7% (2/12) in the 4 mg/kg bid group and 36.4% (4/11) in the 6 mg/kg bid group. Common adverse drug reactions included diarrhea and loose stool. In adverse drug reactions related to laboratory tests one case in the 6 mg/kg bid group showed increased AST and ALT. No cases withdrew from the study due to adverse events. 4. Pharmacokinetics and PK-PD: Pharmacokinetics were examined in 22 cases for whom plasma TBPM concentration could be measured, and increase in C_max and AUC_0-24h were noted as dosage increased. PK-PD parameters in 7 strains in 6 cases analyzed for PK-PD showed 13 to 4,810 for AUCf/MIC, 9 to 3,145 for C_maxf/MIC, and 11 to 100% for T>MIC. 5. Drug compliance: The proportion of cases judged to be "very easy to take" or "easy to take" was 95.7%. In conclusion, clinically recommended dosage and administration of TBPM-PI in the treatment of pediatric acute otitis media and acute upper respiratory tract infection was 4 mg/kg bid.