Vol.57 No.S-1 March 2009

Pharmacokinetics and safety of oral carbapenem antibiotic tebipenem pivoxil tablets in healthy male volunteers

Mitsuyoshi Nakashima¹⁾, Jun Morita²⁾ and Kazumasa Aizawa²⁾

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, safety, and tolerability of tebipenem pivoxil (TBPM-PI), an oral carbapenem antibiotic and TBPM prodrug, in single oral administration of TBPM-PI tablets at 25, 50, 100, 150, 200, 300, 400, 500 and 600 mg (potency) during fasting, and multiple oral administration of TBPM-PI tablets at 100, 200, and 300 (potency) after a meal, t.i.d., for 7 days, and 500 mg (potency) after a meal, b.i.d., for 7 days in healthy male volunteers.
TBPM was mainly detected plasma and urine after oral TBPM-PI administration.
In single oral administration, C_max and AUC_0-∞ increased with dosage from 25 to 500 mg. Cumulative urinary excretion of TBPM from 0 to 24 hours after administration was 50-70%.
In multiple oral administration, C_max and AUC_0-∞ increased with dosage from 100 to 500 mg. Linearity was noted between C_max of TBPM and the TBPM-PI doses from 100 to 200 mg and between AUC_0-∞ of TBPM and TBPM-PI doses from 100 to 500 mg. t_1/2 and urinary excretion of TBPM were constant and TBPM did not accumulate.
In safety and tolerability, side effects after single or multiple oral TBPM-PI administration were mild in severity and resolved without treatment, suggesting no problem in safety.
In conclusion, TBPM-PI rapidly metabolized into TBPM after oral TBPM-PI tablets administration and TBPM was excreted urine. TBPM-PI is expected to be clinically useful due to its favorable pharmacokinetics.

Key word

tebipenem pivoxil, pharmacokinetics, healthy volunteer

Received

October 28, 2008

Accepted

November 25, 2008

Jpn. J. Chemother. 57 (S-1): 82-89, 2009