QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dmd.108.023143v1 37/1/74    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raghavan, N. Articles by Zhang, D. Search for Related Content PubMed PubMed Citation Articles by Raghavan, N. Articles by Zhang, D.

Apixaban Metabolism and Pharmacokinetics after Oral Administration to Humans

Pharmaceutical Candidate Optimization (N.R., K.H., H.Z., W.G.H., D.Z.), Discovery Medicine and Clinical Pharmacology (C.E.F., Z.Y.), Discovery Chemistry and Biology (D.P., S.C., S.B., P.C.W.), Bristol-Myers Squibb Research and Development, Princeton, New Jersey

The metabolism and disposition of [¹⁴C]apixaban, an orally bioavailable, highly selective, and direct acting/reversible factor Xa inhibitor, was investigated in 10 healthy male subjects without (group 1, n = 6) and with bile collection (group 2, n = 4) after a single 20-mg oral dose. Urine, blood, and feces samples were collected from all subjects. Bile samples were also collected for 3 to 8 h after dosing from group 2 subjects. There were no serious adverse events or discontinuations due to adverse effects. In plasma, apixaban was the major circulating component and O-demethyl apixaban sulfate, a stable and water-soluble metabolite, was the significant metabolite. The exposure of apixaban (C_max and area under the plasma concentration versus time curve) in subjects with bile collection was generally similar to that in subjects without bile collection. The administered dose was recovered in feces (group 1, 56.0%; group 2, 46.7%) and urine (group 1, 24.5%; group 2, 28.8%), with the parent drug representing approximately half of the recovered dose. Biliary excretion represented a minor elimination pathway (2.44% of the administered dose) from group 2 subjects within the limited collection period. Metabolic pathways identified for apixaban included O-demethylation, hydroxylation, and sulfation of hydroxylated O-demethyl apixaban. Thus, apixaban is an orally bioavailable inhibitor of factor Xa with elimination pathways that include metabolism and renal excretion.

This article has been cited by other articles:

				D. Zhang, K. He, N. Raghavan, L. Wang, J. Mitroka, B. D. Maxwell, R. M. Knabb, C. Frost, A. Schuster, F. Hao, et al. Comparative Metabolism of 14C-Labeled Apixaban in Mice, Rats, Rabbits, Dogs, and Humans Drug Metab. Dispos., August 1, 2009; 37(8): 1738 - 1748. [Abstract] [Full Text] [PDF]

				L. Wang, N. Raghavan, K. He, J. M. Luettgen, W. G. Humphreys, R. M. Knabb, D. J. Pinto, and D. Zhang Sulfation of O-Demethyl Apixaban: Enzyme Identification and Species Comparison Drug Metab. Dispos., April 1, 2009; 37(4): 802 - 808. [Abstract] [Full Text] [PDF]