INFLUENCE OF METHYLDOPA, BENDROFLUAZIDE AND NIFEDIPINE ON THE PHARMACOKINETICS OF METFORMIN IN TYPE 2 DIABETIC PATIENTS WITH HYPERTENSION
INFLUENCE OF METHYLDOPA, BENDROFLUAZIDE AND NIFEDIPINE ON THE PHARMACOKINETICS OF METFORMIN IN TYPE 2 DIABETIC PATIENTS WITH HYPERTENSION
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Date
2015-09
Authors
BELLO, SANI SA‘IDU
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Abstract
Drug interaction may be the result of various processes, including alterations in the pharmacokinetics of the drug, such as in the absorption, distribution, metabolism and excretion (ADME) or combination of these effects or actions. This study investigated was the effect of methyldopa, bendrofluazide and nifedipine on the pharmacokinetics and pharmacodynamics of metformin in the treatment of type 2 diabetic patients with hypertension. Metformin was administered alone and then co-administered separately with either 250mg methyldopa, 5mg of bendrofluazideor 30mg of nifedipine in the patients. HPLC was used to analyse the blood samples of the subjects using Hypersil C18 column with acetonitrile, methanol and buffer(13:7:80) as mobile phase.The mean maximum absorptionconcentration (Cmax) of metformin changedslightly from 1890.67±0.11ng/ml when administered alone to 1752.17±0.232ng/ml when administered with methyldopa,which is insignificant (P ˃0.05) and decreased to 1865.67±0.002 when administered with bendrofluazide (P ˂0.05) but increased significantly (P ˂0.05) to 2357.16±0.10ng/ml when co-administered with nifedipine all at maximum absorption time (Tmax,) of 3 hrs. AUC 0-8 also increased from 8882.10±0.21ng/ml/h alone to 8895.30 ± 0.22ng/ml/h, (P >0.05) when interacted with methyldopa, 8985.85±0.04ng/ml/h when administered with bendroflazide(P >0.05) and to 10724.57±0.00 ng/ml/h when interacted with nifedipine(P >0.05). AUC 0-∞ also increased in all the three cases but was statistically significant (P <0.05) only when co-administered with nifedipine, from 12106.87±0.01ng/ml/h to 13238.58±0.01ng/ml/h(P <0.05). Similarly, mean blood sugar level of all the patients significantly (P <0.05) increased postprandially,which signified hyperglycemic response. There was also a decrease in blood pressure level of the patients when Metformin was co-administered with methyldopa, bendrofluazide and nifedipine.The resultscompared favorably with the work of other researchers. Nifedipine enhanced metformin concentration significantly (P <0.05) while methyldopa and bendrofluazide did not when co-administered separately. Therefore, co-administration of metformin with nifedipine should be closely monitored in diabetic patients taking the two drugs
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A Thesis submitted to the School of Postgraduate Studies, Ahmadu Bello University, Zaria- Nigeria In partial fulfilment of the requirement for the award of Doctor of Philosophy Degree in Pharmaceutical Chemistry Department of Pharmaceutical and Medicinal Chemistry Ahmadu Bello University, Zaria, Nigeria
Keywords
METHYLDOPA, BENDROFLUAZIDE AND NIFEDIPINE, METHYLDOPA, BENDROFLUAZIDE AND NIFEDIPINE, METFORMIN IN TYPE 2 DIABETIC PATIENTS, HYPERTENSION