DEVELOPMENT OF RP-HPLC METHODS FOR THE ESTIMATION OF NEBIVOLOL AND CARVEDILOL WITH SELECTED NSAIDS AND ITS APPLICATION TO DRUG DISPLACEMENT INTERACTION STUDIES

Drug-drug interactions are gaining importance in practice nowadays. Many drugs bind to serum albumin and alter pharmacokinetics of the drugs such as distribution and elimination. Any small change in the extent of binding will largely affect the plasma concentration, especially those of highly bound drugs. The binding interactions of nebivolol (NEBI) and carvedilol (CAR) with BSA in presence of aceclofenac (ACE) and lornoxicam (LOR) were studied under simulated physiological conditions using validated reversed phase high performance liquid chromatographic (RP-HPLC) methods. The highest percentage protein binding of NEBI and CAR at saturation level were found to be 87.7±0.6% and 81.5±0.6%, respectively. In presence of ACE and LOR the maximum binding was 67.9±3.3% and 75.2±1.6% for NEBI and 80.4±0.03% and 42.0±0.3% for CAR. From the interaction study a significant decrease was observed in the protein binding of two drugs that may lead to increase in their plasma concentrations. Therefore careful monitoring should be exercised during the combination therapy of NEBI with ACE or LOR and CAR with LOR. Further in vivo studies are warranted for both NEBI and CAR in presence of these non-steroidal antiinflammatory drugs (NSAIDs) for which the developed RP-HPLC methods could serve purpose.