FUW TRENDS IN SCIENCE & TECHNOLOGY JOURNAL

(A Peer Review Journal)
e–ISSN: 2408–5162; p–ISSN: 2048–5170

FUW TRENDS IN SCIENCE & TECHNOLOGY JOURNAL

EFFECTS OF METRONIDAZOLE AND AMOXICILLIN ON THE PHARMACOKINETICS OF METFORMIN IN TYPE II DIABETIC PATIENTS
Pages: 309-313
M. A. Garba, M. T. Bakare-Odunola, M. Garba, A. Musa, A. Haruna and R. Bako


keywords: Amoxicillin, diabetes, high performance liquid chromatography, metformin, metronidazole

Abstract

Infection is common in diabetes and in the course of treatment metronidazole and amoxicillin may be co-administered with metformin. The study was designed to evaluate the effects of co-administration of metronidazole tablet and amoxicillin capsule on the pharmacokinetics of metformin in type II diabetic patients. Twelve patients with age ranging from 35 – 55 years, weight 50 – 70 kg and height 1.5 – 1.75 m participated 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 two groups, with six subjects in each group. The first group received a single dose of metformin with metronidazole, while the second group received metformin co-administered with Amoxicillin. Blood samples were collected at 0, 0.5, 1.5, 3.0, 4.0, 6.0 and 8.0 h post drug administration 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 a reversed phase. High performance liquid chromatography (HPLC) method on a C–8column (4.6 x 150 nm), mobile phase acetonitrile/potassium dihydrogen orthophosphate (21:79) and a ultra violet (UV) detector at 236 nm. When metformin was co-administered with metronidazole, Ka increased to 0.59 ± 0.04 h-1, Cmax to 1.38 ± 0.35 µg/ml; while AUC and t1/2β increased to 536.71 ± 0.02 µgh/ml and 6.2 ± 0.02 h, respectively. These increments were found to be significant (p < 0.05). On the other hand, when metformin was co-administered with amoxicillin most of the changes were not significant (p > 0.05).

References

Bailey CJ 2012. Biguanides and NIDDM. Diabetes Care., 15(6): 755-772. Bakare-Odunola MT, Garba M, Enemali SI, Okeniyi SO & Gebi J 2001. The influence of ampicillin/cloxacillin on the of chlorpropamide in Type 2 diabetic Patients. West African J. Pharmac.., Drug Res., 17(1 & 2): 74-76. Bhavesh D, Chetan G, Bhat1 KM & Shivprakash I 2007. Estimation and pharmacokinetics of metformin in human volunteers. Indian J. Pharm. Educ. Res., 41(2): 127-135. Burger ASV and Mitchell JF (eds) 2012. General Pharmacology, kinetics and sulphonylureas.In: Gaddum pharmacology. Oxford University Press, London. PP17, 162-201. Bonfigli AR, Manfrini S, Gregorio F, Testa R, Testa I, Sio G & Coppa G. 2013. Determination of plasma Metformin by new cation exchange HPLC technique. Ther. Drug Monit., 21(3): 330-334. Cheng CL, Chou CH 2001. Determination of Metformin in human plasma by High performance liquid chromatography with spectrophotometric determination. J. Chromatogr B. Biomed Sci. Appl., 762(1): 51-58. Denno KM & Saddle TW 2009. Effects of biguanidine class of oral hypoglycemic agents on mouse embryogenesis. Teratology., 49(4): 260-266. Eileen YY, Michael PM, Helen L, Mei Z & Evan JB 2009. A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM. British J. Clinical Pharmac., 67(1): 130–131. Garba M, Bakare-Odunola MT, Obodozie O, Bello K & Okeniyi SO 1999. The influence of Metronidazole on the pharmacokinetic profile of chlorpropamide in Type II Diabetic patients. J. Pharmac. Res. and Dev., 4: 95-100. Hermann LS 2010. Clinical pharmacology of biguanides. In: Kulhmann I, Plus W editor.Hand Book of Experimental Pharmacology.Hiedelberg: Springer Veelog, pp. 374 - 407. Hermann LS 2013. Metformin: a review of its pharmacological properties and therapeutic use. Diabete Metab., 5(3): 233-45. Pentikainen PJ, Neuvonen PJ & Pentilla A 2010. Pharmacokinetics of Metformin after Intravenous and oral administration to man. Eur. J. Clin. Pharmacol., 16(3): 683- 693. Tucker GT, Casey C, Philips PJ, Con nor H, Ward JD, Wooda HF 2010. Metformin kinetics in healthy subjects and in patients with diabetes mellitus. British J. Clin. Pharmac., 12(2): 235-246. Vesterqvist O, Nabbie F & Swanson B 2014. Determination of metformin in plasma by high performance liquid chromatography after ultrafiltration. J. Chromatogr B. Biomed Sci. Appl., 716(1-2): 299-304. Zarghi A, Foroustan SM, Shafaati A & Khoddam A 2003. Rapid determination of Metformin in human plasma using ion-pair HPLC. J. Pharm Biomed Anal., 31(1): 197-200. Zhang M, Moore GA, Lever M, Gardiner SJ, Kirkpatric CM & Begg EJ 2002. Rapid and simple high-performance liquid chromatography assay for the determination of Metformin in human plasma and breast milk. J. Chromatogr B Analyt Technol Biomed Life Sci., 766(1): 175-179. Zhouping W, Zhujan Z, Zhifeng F, Wanfen L & Xiao Z 2001. Sensitive flow injection hemiluminescence determination of Metformin based on N-Bromosuccinimide flourescein system. Analytical Letters, 36(12): 2683-2697.

Highlights