Vol.57 No.S-1 March 2009
Pharmacokinetics and safety of tebipenem pivoxil fine granules, an oral carbapenem antibiotic, in healthy male volunteers
1)Hamamatsu Institute of Clinical Pharmacology & Therapeutics, 40-3 Sukenobu, Naka-ku, Hamamatsu, Shizuoka, Japan
2)Clinical Research Department, Meiji Seika Kaisha, LTD.
Abstract
We assessed the pharmacokinetics, metabolism, and safety of the oral carbapenem antibiotic tebipenem pivoxil(TBPM-PI), a TBPM prodrug, after a single oral administration, at 100, 200 and 400 mg (potency) in healthy male volunteers.
TBPM-PI was quickly absorbed and metabolized into TBPM, an active metabolite, that was mainly excreted in urine. In plasma and urine, TBPM was mostly detected and the TBPM opened ring (LJC11,562) was quantified at a low concentration compared to TBPM. Neither the TBPM-PI nor TBPM-PI opened ring was detected in plasma or urine. Total urinary excretion of TBPM and the LJC11,562 metabolite was 70-80%, indicating high oral TBPM-PI absorption. In feces, only LJC11,562 was quantified at 2% of the TBPM dose.
TBPM Cmax increased dose-dependently from 100 to 400 mg (potency) after TBPM-PI fine granules administration. Linearity was shown between AUC0-∞ of TBPM and TBPM-PI dose.
In conclusion, TBPM-PI fine granules showed high oral absorption, and TBPM-PI was quickly metabolized into the active metabolite TBPM. It was rarely metabolized, and excreted into urine. TBPM-PI fine granules with these favorable pharmacokinetics are thus expected to be clinically useful.
Key word
tebipenem pivoxil, pharmacokinetics, healthy volunteer
Received
October 15, 2008
Accepted
December 12, 2008
Jpn. J. Chemother. 57 (S-1): 90-94, 2009
