Vol.57 No.S-1 March 2009
Effect of probenecid or diet on tebipenem pivoxil tablets pharmacokinetics 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 effect of probenecid on the pharmacokinetics of tebipenem pivoxil(TBPM-PI), an oral carbapenem antibiotic and TBPM prodrug, in healthy male volunteers. We also studied the effect of diet on TBPM-PI tablets pharmacokinetics in clinical dosage.
TBPM-PI tablets of 250 mg (potency) were administered in combination with 1 g probenecid. We observed increased AUC0-∞ and Cmax of TBPM, decreased apparent total clearance, renal clearance, and urinary excretion of TBPM and prolonged t1/2 of TBPM considered attributable to the inhibitory effect of probenecid on renal tubular TBPM secretion.
For dietary effect, we compared the pharmacokinetics of TBPM-PI tablets at 250 mg (potency) during fasting and nonfasting. TBPM Cmax in the nonfasting was 80% of that in the fasting, AUC0-∞ and urinary excretion were comparable in fasting and nonfasting.
We concluded that appropriate dose and regimen are recommended when TBPM-PI is administered with drugs such as probenecid that inhibit tubular secretion, given that such drugs influence TBPM-PI pharmacokinetics. Diet intake influenced TBPM-PI tablets pharmacokinetics only negligibly, if at all.
Key word
tebipenem pivoxil, probenecid, pharmacokinetics, food, drug interaction
Received
October 15, 2008
Accepted
December 12, 2008
Jpn. J. Chemother. 57 (S-1): 103-108, 2009
