Pharmacokinetic interaction between telithromycin and metformin in diabetes mellitus rats

Telithromycin and metformin have been reported to be commonly metabolized via hepatic CYP3A1/2 in rats. Community-acquired respiratory tract infection was reported to be frequent in patients with diabetes mellitus. Compared with controls, hepatic CYP3A1/2 was reported to be increased in male rats with diabetes mellitus induced by streptozotocin (DMIS rats). After the intravenous administration of both drugs together to male DMIS rats, the time-averaged non-renal clearance (CLNR) of metformin was significantly slower (by 33.1%; 10.3 versus 15.4ml min^-1 kg^-1) than metformin alone due to the inhibition of hepatic metabolism of metformin by telithromycin via CYP3A1/2. After the oral administration of both drugs together, the total area under the plasma concentrationtime curve (AUC) of metformin was comparable possibly due to the increased intestinal metabolism of metformin by telithromycin.