BIOANALYTICAL METHOD DEVELOPMENT FOR SIMULTANEOUS DETERMINATION OF DRUGS ACTING ON CYTOCHROME P450 ENZYME DRUG INTERACTION STUDY

Abstract

quotOBJECTIVES: The specific objectives are to develop a bioanalytical method for drugs acting on cytochrome P450 enzymes, apply the validated method for the evaluation of selected drugs in patient plasma samples using RP-HPLC, assess the pharmacokinetic behavior of the drugs selected and to evaluate the various biochemical parameters and pharmacological activities exerted by the drugs in patient samples justifying the drug-drug interaction. newlineMETHODOLOGY: The bioanalytical method of the selected drugs individually and in combination was developed using blank human plasma spiked with the drugs using reverse phase high performance liquid chromatography (RP-HPLC). The possible drug-drug interactions between the selected classes of drugs acting on cytochrome P450, the plasma samples of patients were subjected to RP-HPLC analysis. Platelet count and platelet aggregation were determined. Lipid profile estimation was done for the patients who were on statins alone and those with clopidogrel in presence of statins respectively. newlineRESULTS: A simple, sensitive and accurate method was developed. Results indicate that, in the patient plasma samples the concentration of clopidogrel in presence of omeprazole and atorvastatin decreases drastically and prominently when compared to patients who are on pantoprazole and rosuvastatin. Among the 61 samples studied, a total of only 9 samples were found to have a low platelet count by both the methods. In-spite of presence of dual antiplatelets, the patient s coadministration with PPI s showed high platelet count. The aggregation study showed that clopidogrel is less effective in inhibiting platelet aggregation when co-administered with PPI s and Statins, a CYP2C19 and CYP3A4 substrates. newlineCONCLUSION: The study indicated that the pharmacokinetic parameters were determined for the patient plasma prescribed with dual antiplatelet therapy along with PPI s and statins using the validated bioanalytical method to understand the extent of drug-drug interactions. newlinequot newline