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 (CL(NR)) of metformin was significantly slower (by 33.1%; 10.3 versus 15.4 ml 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 concentration-time curve (AUC) of metformin was comparable possibly due to the increased intestinal metabolism of metformin by telithromycin.
Lee
J H
JH
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea. leemg@snu.ac.kr
Kang
H E
HE
Lee
M G
MG
D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003956:Dialysis; D004347:Drug Interactions; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D048628:Ketolides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008862:Microsomes, Liver / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
D001798:Blood Proteins; D048628:Ketolides; D008687:Metformin; C106791:telithromycin