Influence of Metronidazole on the Pharmacokinetics of Metformin in Type II Diabetic Patients

Abstract

Infection is common in diabetes and metronidazole is often co-administered with metformin. This study is therefore to examine the influence of concomitant administration 400 mg dose metronidazole tablet with (2x500mg) metformin on pharmacokinetic parameters of metformin in type II diabetic Patients. The approval for the research was granted by the Ethical Committee of Ahmadu Bello University Teaching Hospital Zaria, Nigeria. Six Type II diabetic patients with age ranging from 25-55 years, weight from 50-70 kg took part in the study. Each of the six patients received the following treatment at two weeks intervals; Metformin tablet (1gm alone and concomitantly with 400 mg metronidazole tablets. Blood samples were collected at interval of 0 to 8 hours and stored at -4⁰C before analysis. High performance liquid chromatography (HPLC) was adopted, modified and validated to measure the plasma levels of metformin in the samples. Samples were chromatographed on Agilent Technologies 1120 Compact LG model of HPLC, on column Eclipse x BD C-8,4.6 x 150 nm for metformin with mobile phase acetonitrile: potassium dihydrogen orthophosphate (79:21) with flow rate of 1.50 mL/min, using UV detector. The results obtained altered the pharmacokinetic parameters of metformin significantly. The highest plasma concentration increased from 1140.43±0.52 to 1326.67±0.4 ng/ml at T_max 3.0 hours, with increase in area under the plasma concentration – time curve from 4388.81±0.52 to 5361.84±0.80 ng/ml/h. Significant decrease in volume of distribution from 333852.19±0.87  to 313, 061.43 ± 0.02ml was also observed. The results showed that metronidazole has potentiation effect on the disposition of metformin when concomitant administered to type II diabetic patients. Diabetic patients who require metronidazole needs adjustment of dosage regimen to avoid the risk of toxicity.