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Endoxifen, a New Cornerstone of Breast Cancer Therapy: Demonstration of Safety, Tolerability, and Systemic Bioavailability in Healthy Human Subjects
Author(s) -
Ahmad A,
Shahabuddin S,
Sheikh S,
Kale P,
Krishnappa M,
Rane R C,
Ahmad I
Publication year - 2010
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 - 10.1038/clpt.2010.196
Subject(s) - tolerability , bioavailability , pharmacokinetics , medicine , pharmacology , tamoxifen , active metabolite , drug , cyp2d6 , breast cancer , metabolite , pharmacogenomics , cancer , adverse effect , cytochrome p450 , metabolism
Endoxifen is an active metabolite of tamoxifen, a drug used in the treatment of breast cancer. In order to be clinically effective, tamoxifen must be converted to endoxifen by cytochrome P450 2D6 (CYP2D6). A study involving single escalating oral doses was conducted in humans to evaluate the safety, tolerability, and pharmacokinetics (PK) of endoxifen. This is the first study demonstrating that single oral doses of endoxifen are safe and well tolerated and have sufficient bioavailability to reach systemically effective levels in human subjects. Furthermore, it was found that endoxifen is rapidly absorbed and systemically available and that it displays dose proportionality in peak drug concentrations in plasma ( C max ) and area under the concentration–time curve extrapolated from 0 to ∞ (AUC 0–∞ ) over the dose range 0.5–4.0 mg. Clinical Pharmacology & Therapeutics (2010) 88 6, 814–817. doi: 10.1038/clpt.2010.196