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ABSTRACT:
The aim of this study was to predict the blood/plasma drug concentration profiles for five brand of nifedipine present on the Saudi Arabia market by using the numerical convolution method and to estimate the pharmacokinetic parameters (Cmax, Tmax, Ka, K and Vd) by the application of the residual method to the predicted plasma drug concentration profiles. Results showed that the higher Cmax was 118.95ng/ml for brand A2 and the lower Cmax was 72.29ng/ml for brand A3. The Tmax was ranged from 2.3 hr to 4.9 hr for brands A2 and A3 respectively. The total area under plasma drug concentration curve (AUCinf.) was in lower value equal to 585.59 ng x hr/ml for brand A2 and the higher value was for brand A5 equal to 743.52ng x hr/ml. The volume of distribution was also increased from 52.5 L for free nifidipine to 72 L for brand A1. The predicted first order elimination rate constant was decreased from 0.34 hr-1 for free nifedipine to 0.17 hr-1 for brand A3. The half-life of nifedapine was increased from 2 hours for free drug to 3.93 hours for brand A3. From this study it can be concluded that brands present in the market that shows similarity in accordance to the Dissimilarity factor f1 are not always guaranty that they will be bioequivalent in vivo and vice versa. Also, this study indicates that the method of convolution is a useful tool for prediction of bioequivalence of different brands present on the market.
KEYWORDS: Convolution method, pharmacokinetic parameters, nifedipine, dissolution profiles.
INTRODUCTION:
Nifedipine is a calcium channel blocking agent [Dimethyl-2,6-methyl-4-)2-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate] class II in the Biopharmaceutics Classification System (BCS) with limited absorption from the gastrointestinal tract due to its poor solubility in water. Nifedipine is highly recommended in the management of angina pectoris and systemic hypertension due to better tolerance by patients1,2,3,4,5.
Previous studies reported that extended-release dosage forms of nifedipine showed less side effects from immediate release dosage forms by reducing the appearance of steep rises in plasma concentration of the drug that increase heart rate in case of immediate release formulations6,7.
The physical quality and the dissolution kinetics of commercially available extended-release dosage forms of nifedipine were extensively investigated. Previous studies based on dissolution profiles comparison...