title: [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 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.
authors.affiliation: Apotheke, Universitätsklinikum Tübingen, Röntgenweg 9, 72076, Tübingen, Deutschland. hans-peter.lipp@med.uni-tuebingen.de.
authors.forename: H-P
authors.initials: HP
authors.lastname: Lipp
authors.affiliation: Urologie, Charité, Berlin, Deutschland.
authors.forename: K
authors.initials: K
authors.lastname: Miller
mesh_terms: D000069501:Abiraterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001549:Benzamides; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000556:secondary*; D004347:Drug Interactions; D019317:Evidence-Based Medicine; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D000069501:Abiraterone Acetate
keywords: Cytochrome P450 enzyme system; Drug interactions; Multimorbidity; Pharmacokinetics; Polypharmacy