Abstract | PURPOSE: 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:
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Authors | K N Chi, A Tolcher, P Lee, P J Rosen, C K Kollmannsberger, K P Papadopoulos, A Patnaik, A Molina, J Jiao, C Pankras, B Kaiser, A Bernard, N Tran, M Acharya |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 71
Issue 1
Pg. 237-44
(Jan 2013)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 23064959
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
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Chemical References |
- Androstadienes
- Dextromethorphan
- Theophylline
- CYP1A2 protein, human
- Cytochrome P-450 CYP1A2
- Cytochrome P-450 CYP2D6
- Abiraterone Acetate
- Prednisone
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Topics |
- Abiraterone Acetate
- Androstadienes
(administration & dosage, adverse effects, pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, adverse effects, pharmacology)
- Area Under Curve
- Cytochrome P-450 CYP1A2
(drug effects, metabolism)
- Cytochrome P-450 CYP2D6
(drug effects, metabolism)
- Dextromethorphan
(administration & dosage, pharmacokinetics)
- Drug Interactions
- Follow-Up Studies
- Humans
- Male
- Neoplasm Metastasis
- Prednisone
(administration & dosage, pharmacology)
- Prostatic Neoplasms
(drug therapy, pathology)
- Theophylline
(administration & dosage, pharmacokinetics)
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