Vol.57 No.4 July 2009
Pharmacological properties and clinical performance of the novel oral carbapenem antimicrobial drug, "Tebipenem pivoxil" (Orapenem® fine granules 10% for pediatric use)
Laboratory of Infectious Diseases Science, Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, Japan
Abstract
Tebipenem pivoxil(TBPM-PI, Orapenem® fine granules 10% for pediatric use) is a novel oral carbapenem antimicrobial drug that received approval for manufacture and marketing in Japan on April 22, 2009. Tebipenem(TBPM), the active ingredient of TBPM-PI, has a wide antimicrobial spectrum, and strong antimicrobial power; it has particularly strong antimicrobial power against penicillin-resistant Streptococcus pneumoniae and Haemophilus influenzae. The results of a pharmacokinetics-pharmacodynamics(PK-PD) study in a mouse thigh infection model showed that it also had a higher correlation with AUCf/MIC than the correlation of β-lactams with T>MIC.
The PK-PD theory was used in the clinical development of TBPM-PI. Dosage and administration were thus set using the PK-PD theory, and the appropriatness of the setting was confirmed by efficacy evaluation and PK-PD analysis. A dosage and administration confirmation study was conducted in adults after setting the adult dosage and administration based on the AUCf/MIC values obtained in a mouse PK-PD study, and the recommended clinical dosage and administration in adults were obtained. Then, based on weight conversion from adults and PK-PD analysis, the pediatric dosage and administration were set. High clinical efficacy was obtained at the recommended pediatric dosage and administration of 4 mg (potency)/kg b.i.d., and treatment with a high dose of 6 mg (potency)/kg b.i.d. showed high clinical efficacy in refractory cases. Also, in a double-blind comparative study with high-dose CDTR-PI targeting pediatric acute otitis media, the noninferiority to high-dose CDTR-PI was verified, and early bacteriological efficacy was demonstrated to be high. The safety profile was not different from that of existing β-lactam antimicrobial drugs, and there were no clinically problematic adverse effects.
There are strong expectations for TBPM-PI in the treatment of drug-resistant pediatric infections. However, since it is the first oral carbapenem antimicrobial drug, it should not be prescribed too routinely from the viewpoint of preventing the emergence of resistant bacteria, and the indicated diseases should be narrowed down to the three diseases of refractory pediatric otitis media, sinusitis, and pneumonia due to drug-resistant bacteria. It is also appropriate to limit its use to cases in whom standard therapeutic antimicrobial drugs are not expected to be effective.
Key word
tebipenem pivoxil, child, oral carbapenem, PK-PD
Received
May 25, 2009
Accepted
June 18, 2009
Jpn. J. Chemother. 57 (4): 279-294, 2009
