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Aim: A simple and rapid HPLC technique was developed and validated to simultaneously estimate enzalutamide (ENZ) and repaglinide (REP) in rat plasma. Methods: In silico predictions using DDinter and DDI-Pred indicated possible drug-drug interactions between ENZ and REP. A central composite design was used to identify factors influencing the separation of the drugs. Interactions between chromatographic parameters were studied through 51 experiments, followed by illustration with three-dimensional response surface plots. The four factors optimized for the separation of the two drugs are column temperature (A), % organic strength (B), pH (C) and column type (D). Results: Plate count(R1), tailing factor (R2) and resolution (R3) responses in the experimental design were analyzed with the favorable chromatographic conditions predicted to be 0.1% formic acid and acetonitrile as mobile phases on a Phenomenex C18 LC column (250 × 4.6 mm, 5 µm). The method was applied to estimate the drugs in rat plasma using a simple protein-precipitation step and found to be linear, accurate and precise within the ranges of 0.5-16 and 5-50 µg/ml for ENZ and REP, respectively. Conclusion: The optimized method can be used in future bioanalytical workflow for drug quantification and drug-drug compatible studies.

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A novel protocol is developed towards the preparation of alkylated ketones from alcohols in presence of catalytic amount of SmI2 and base with the elimination of water as a single by-product under microwave irradiation conditions. Furthermore, applicability of this methodology to the synthesis of Donepezil and late-stage functionalization in Pregnenolone is also reported. Successful application of this methodology in Friedländer quinolone synthesis using 2-aminobenzyl alcohol and various acetophenones expand the synthetic utility of this protocol.

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Pharmacokinetic drug-drug interaction is a significant safety and efficiency concern as it results in considerable concentration changes. Drug-drug interactions are a substantial concern in anticancer drugs that possess a narrow therapeutic index. These interactions remain as the principal regulatory obstacle that can lead to termination in the preclinical stage, restrictions in the prescription, dosage adjustments or withdrawal of the drugs from the market. Drug metabolizing enzymes or transporters mediate the majority of clinically relevant drug interactions. Cancer diagnosed aged patients use multiple medications and are more prone to significant drug-drug interactions. This review provides detailed information on clinically relevant drug-drug interactions resulting from drug metabolism by enzymes and transporters with a particular emphasis on recent FDA approved antiprostate cancer drugs.

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