Influence of ampicllin/cloxacilin combination on pharmacokinetics of metformin in type II diabetic patients

Abstract

Infection is common in diabetes and ampicillin/cloxacillin combination (Ampiclox®) is often coadministered with metformin. The study examined the influence of concomitant administration of a single dose of (2 x 500 mg) capsules of Ampiclox with (2 x 500 mg) metformin on the pharmacokinetics of the latter 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 ages ranging from 25 - 55 years, weight from 50-70 kg took part in the study. Each of the six patients received the following treatments at two weeks intervals: 1 gm of metformin tablets alone and concomitantly with Ampiclox capsules. Blood samples were collected at intervals of 0 to 8 h 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), using UV detector. The results obtained from the study indicated a statistically significant (P < 0.5) increase in the plasma concentration (C_max) of metformin from 1140.43±0.52 to 1,379.55±0.4 ng/ml at T_max 3.0 h, AUC_{0- 8}hrs from 4388.81±0.52 to 5179.71±0.80 ng/ml/hr and elimination half-life t_1/2β from 3.8 to 5.1 hr^-1. Statistically significant decrease in volume of distribution from 333,852.19.28 ± 0.27 to 283,061 ± 0.02 ml was also recorded. Ampiclox must have inhibited the renal secretion of metformin resulting in higher circulating plasma concentrations. Patients on metformin who require Ampiclox , need therefore to be monitored to avoid therapeutic failure.

Keywords: Ampiclox^®, Diabetes, HPLC, Metformin, Pharmacokinetics