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Pharmacokinetic interaction between telithromycin and metformin in diabetes mellitus rats

J H Lee1, H E Kang, M G Lee

  • 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea. leemg@snu.ac.kr

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
|December 31, 2009
PubMed

Insights

Telithromycin significantly slowed metformin

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Diabetes Mellitus Research

Background:

  • Telithromycin and metformin are metabolized by hepatic CYP3A1/2.
  • Diabetes mellitus can increase hepatic CYP3A1/2 activity in rats.
  • Community-acquired respiratory tract infections are common in diabetic patients.

Purpose of the Study:

  • To investigate the pharmacokinetic interaction between telithromycin and metformin in diabetic rats.
  • To assess the impact of diabetes-induced changes in CYP3A1/2 on drug metabolism.

Main Methods:

  • Male streptozotocin-induced diabetic rats (DMIS rats) were used.
  • Intravenous and oral co-administration of telithromycin and metformin.
  • Measurement of metformin's non-renal clearance (CL(NR)) and area under the plasma concentration-time curve (AUC).

Main Results:

  • Intravenous co-administration resulted in a 33.1% slower CL(NR) of metformin, indicating hepatic metabolism inhibition by telithromycin.
  • Oral co-administration showed a comparable AUC for metformin, potentially due to increased intestinal metabolism.

Conclusions:

  • Telithromycin inhibits the hepatic metabolism of metformin in diabetic rats.
  • The route of administration influences the overall pharmacokinetic interaction between telithromycin and metformin.

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