Effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan and theophylline in patients with metastatic castration-resistant prostate cancer.
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Chi KN, Tolcher A, Lee P, Rosen PJ, Kollmannsberger CK, Papadopoulos KP, Patnaik A, Molina A, Jiao J, Pankras C, Kaiser B, Bernard A, Tran N, Acharya M
Effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan and theophylline in patients with metastatic castration-resistant prostate cancer.
Cancer Chemother Pharmacol. 2013 Jan;71(1):237-44. doi: 10.1007/s00280-012-2001-0. Epub 2012 Oct 12.
- PubMed ID
- 23064959 [ View in PubMed]
- Abstract
PURPOSE: To assess the effect of abiraterone acetate plus prednisone on the pharmacokinetics of dextromethorphan HBr (CYP2D6 substrate) and theophylline (CYP1A2 substrate) in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Men with progressive metastatic mCRPC who failed gonadotropin-releasing hormone therapy and >/=1 lines of chemotherapy were enrolled. Patients received two doses of dextromethorphan HBr-30 mg (n = 18; group A) or theophylline-100 mg (n = 16; group B) under fasting conditions; one dose on cycle 1, day -8, and the other dose on cycle 1, day 8. Only patients with extensive CYP2D6 metabolizing status were assigned to group A. All patients received continuous daily oral abiraterone acetate (1,000 mg) plus prednisone (10 mg) starting on cycle 1, day 1. RESULTS: Coadministration of abiraterone acetate plus prednisone increased the systemic exposure of dextromethorphan by approximately 100%. Ratios of geometric means for maximum plasma concentration (C(max)) (275.36%) and area under plasma concentration-time curves from time 0 to 24 h (AUC(24h)) (268.14%) of dextromethorphan were outside the bioequivalence limit. The pharmacokinetics of theophylline was unaltered following coadministration of abiraterone acetate plus prednisone. Ratios of geometric means [C(max); 102.36% and AUC(24h); 108.03%] of theophylline exposure parameters were within the bioequivalence limit. The safety profile of abiraterone acetate was consistent with reported toxicities. CONCLUSION: Abiraterone acetate plus prednisone increased the exposure of dextromethorphan, suggesting a need for caution when coadministrating with known CYP2D6 substrates. The pharmacokinetics of theophylline was unaffected when coadministered with abiraterone acetate plus prednisone.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Abiraterone Cytochrome P450 2D6 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcenocoumarolAbiraterone The serum concentration of Acenocoumarol can be increased when it is combined with Abiraterone. AcetaminophenAbiraterone The serum concentration of Acetaminophen can be increased when it is combined with Abiraterone. AcyclovirAbiraterone The serum concentration of Acyclovir can be increased when it is combined with Abiraterone. AgomelatineAbiraterone The serum concentration of Agomelatine can be increased when it is combined with Abiraterone. AlbendazoleAbiraterone The serum concentration of Albendazole can be increased when it is combined with Abiraterone.