EFFECTS OF AMPICLOX (AMPICILLIN/CLOXACILLIN), METRONIDAZOLE AND AMOXICILLIN ON THE PHARMACOKINETICS OF METFORMIN IN TYPE 2 DIABETIC PATIENTS
EFFECTS OF AMPICLOX (AMPICILLIN/CLOXACILLIN), METRONIDAZOLE AND AMOXICILLIN ON THE PHARMACOKINETICS OF METFORMIN IN TYPE 2 DIABETIC PATIENTS
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Date
2015-11
Authors
GARBA, MUSA ABDULLAHI
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Abstract
Infection is common in diabetes and in the course of treatment;ampiclox, metronidazole andamoxicillin may be co-administered with metformin for treatment. This study was therefore designed to evaluate the effects of co-administration of ampiclox, metronidazole and amoxicillin on the pharmacokinetics of metformin in type 2 diabetic patients. Eighteen patients with age 25-55 years, weight range 50-70 kg, and height 1.5-1.75 m took part in the study. The study was divided into two phases with a washout period of seven days between the phases. In phase one,metformin alone was administered to all the subjects with 150 ml of water after an overnight fasting. In phase two, the subjects were divided into three groups, with six subjects ineach group. The first group received a single dose ofmetformin with ampiclox, thesecond group receivedmetformin co-administered with metronidazole and the third group received metformin with amoxicillin. Blood samples were collected at interval of 0, 0.5, 1.5, 3.0, 4.0, 6.0 and 8.0 hours and stored at -40C before analysis. Plasma was obtained from the blood and the drug was extracted from the plasma using three times its volume of acetonitrile. The samples were analyzed for metformin using HPLC method on a reversed phase column C-8,4.6 x 150 nm, mobile phase acetonitrile/potassium dihydrogen orthophosphate (21:79), and aUV detector at 236 nm.
The absorption rate constant(Ka), mean peak plasma concentration (Cmax), area under the curve (AUC), elimination half-life (t1/2β) of metformin alone were 0.46±0.04 hr-1, 1,140.43±0.52, 4,388.72 ±0. 71and 3.8±0.07 hr-1respectively. When metformin was co-administered withampiclox,Ka increased to 0.58 ±0.04, Cmax to 1.28 ±0.35 μg/ml, while
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AUC and t1/2β increased to 5,179.71 ±0.02 and 6.2± 0.02 respectively. When metformin was co-administered with metronidazole,Ka increasedto 0.59 ±0.03 and Cmaxto 1.35±0.42 μg /ml, while AUCand t 1/2β increased to 5,179.71 ±0.02 and 6.2± 0.02 hr-1 respectively. All these increases were found to be significant (p < 0.05). No significant (p< 0.05) changes were observed when metformin was co-administered with amoxicillin. The findings indicated that ampiclox and metronidazole may have potentiating effects on the hypoglycemicaction of metformin. Consequentlydiabetic patients who require ampiclox and /or metronidazole in addition to metformin may need adjustment of dose regimen to avoid the risk of toxicity.
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A DISSERTATION SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES, AHMADU BELLO UNIVERSITY ZARIA, NIGERIA IN PARTIAL FULFILLMENT FOR THE AWARD OF DOCTOR OF PHILOSOPHY IN PHARMACEUTICAL CHEMISTRY DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL CHEMISTRY, FACULTY OF PHARMACEUTICAL SCIENCES, AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA
Keywords
EFFECTS,, AMPICLOX,, AMPICILLIN/CLOXACILLIN,, METRONIDAZOLE,, AMOXICILLIN, PHARMACOKINETICS,, METFORMIN,, TYPE 2 DIABETIC PATIENTS,