Sulfation of O-Demethyl Apixaban: Enzyme Identification and Species Comparison

• Published in: Drug metabolism and disposition Vol. 37; no. 4; pp. 802 - 808
• Main Authors: Wang, Lifei, Raghavan, Nirmala, He, Kan, Luettgen, Joseph M, Humphreys, W Griffith, Knabb, Robert M, Pinto, Donald J, Zhang, Donglu
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.04.2009
• Subjects: Animals; Biocatalysis; Biotransformation; Chromatography, High Pressure Liquid; Enzyme Inhibitors - pharmacology; Humans; Mass Spectrometry; Methylation; Pyrazoles - metabolism; Pyrazoles - pharmacokinetics; Pyridones - metabolism; Pyridones - pharmacokinetics; Species Specificity; Sulfates - metabolism; Sulfotransferases - antagonists & inhibitors; Sulfotransferases - metabolism

Apixaban, a potent and highly selective factor Xa inhibitor, is currently under development for treatment of arterial and venous thrombotic diseases. The O -demethyl apixaban sulfate is a major circulating metabolite in humans but circulates at lower concentrations relative to parent in animals. The...