Treatment of metastatic castration-resistant prostate cancer : Drug interaction potentials of abiraterone acetate and enzalutamide

Abstract

With an ageing population and associated increasing multimorbidity and polypharmacy, the potential for drug-drug interactions (DDIs) becomes increasingly important. In general, DDIs are more likely to be clinically significant for drugs with anarrow therapeutic index, necessitating dosage adjustments or replacement of co-administered drugs. Many DDIs are aresult of pharmacokinetic interactions of the cytochrome P450 enzymes. In particular, the CYP3A4 isoenzyme is involved in the metabolism of about 50 % of currently used drugs. Accordingly, many commonly used drugs in patients with prostate cancer are substrates of Cyp3A4. Hence enzalutamide, astrong Cyp3A4 inductor, has the potential to substantially decrease plasma concentrations and the effects of many co-medications in this patient population, whereas abiraterone acetate, astrong Cyp2D6 inhibitor, is less of aconcern with respect to Cyp450 inhibition, since the Cyp2D6-mediated metabolism is much smaller and Cyp2D6 substrates are prescribed to alesser extent in patients with prostate cancer.