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Lack of effect of ketoconazole on the pharmacokinetics of oral bexarotene in healthy subjects
Author(s) -
Kuan H.,
Loewen G.,
Geiser R.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.174
Subject(s) - bexarotene , ketoconazole , pharmacokinetics , pharmacology , crossover study , cyp3a4 , medicine , clinical pharmacology , chemistry , cytochrome p450 , dermatology , metabolism , antifungal , biochemistry , alternative medicine , pathology , nuclear receptor , transcription factor , gene , placebo
Background/Aims Bexarotene, a synthetic retinoid indicated for the treatment of cutaneous T‐cell lymphoma, is a substrate of cytochrome P4503A4 (CYP3A4). This study was aimed to assess the effect of ketoconazole, a potent CYP3A4 inhibitor, on the pharmacokinetics of orally administered bexarotene. Methods This was an open‐label, two‐treatment, two‐period, two‐sequence randomized crossover study. Twenty‐four healthy subjects (23 men and 1 woman) between 18 and 65 years old were enrolled. Each subject was given bexarotene as two single 400 mg/m 2 doses: alone in Period 1 and during a 6‐day ketoconazole 400 mg once daily regimen in Period 2. Venous blood samples were collected for up to 72 hours after each bexarotene administration. Bexarotene plasma concentrations were determined using a validated assay. Results The bexarotene+ketoconazole to bexarotene alone ratios of geometric mean values were 92.19% and 92.46% for the area under the concentration‐time curve and the maximum plasma concentration, respectively. The corresponding 90% confidence intervals for both parameters were within the 80% to 125% boundaries. Conclusion Multiple‐dose ketoconazole did not affect single‐dose bexarotene pharmacokinetics to a clinically important extent, indicating that bexarotene can be coadministered with CYP3A4 inhibitors. Clinical Pharmacology & Therapeutics (2005) 77 , P74–P74; doi: 10.1016/j.clpt.2004.12.174