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

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 a narrow therapeutic index, necessitating dosage adjustments or replacement of co-administered drugs. Many DDIs are a result 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, a strong Cyp3A4 inductor, has the potential to substantially decrease plasma concentrations and the effects of many co-medications in this patient population, whereas abiraterone acetate, a strong Cyp2D6 inhibitor, is less of a concern with respect to Cyp450 inhibition, since the Cyp2D6-mediated metabolism is much smaller and Cyp2D6 substrates are prescribed to a lesser extent in patients with prostate cancer.