• Xiaoli Wang, Sabiha Mondal, Jessie Wang, Giridhar Tirucherai, Donglu Zhang, Rebecca A Boyd, and Charles Frost.
• Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Mail Stop E13-08, Route 206 and Province Line Road, Princeton, NJ, 08543-4000, USA.
• Am J Cardiovasc Drugs. 2014 Apr 1; 14 (2): 147-54.

BackgroundActivated charcoal is commonly used to manage overdose or accidental ingestion of medicines. This study evaluated the effect of activated charcoal on apixaban exposure in human subjects.MethodsThis was an open-label, three-treatment, three-period, randomized, crossover study of single-dose apixaban (20 mg) administered alone and with activated charcoal given at 2 or 6 h post-dose to healthy subjects. Blood samples for assay of plasma apixaban concentration were collected up to 72 h post-dose. Pharmacokinetic parameters, including peak plasma concentration (Cmax), time to Cmax (Tmax), area under the concentration-time curve from time 0 to infinity (AUCINF), and terminal half-life (T½), were derived from apixaban plasma concentration-time data. A general linear mixed-effect model analysis of Cmax and AUCINF was performed to estimate the effect of activated charcoal on apixaban exposure.ResultsA total of 18 subjects were treated and completed the study. AUCINF for apixaban without activated charcoal decreased by 50 and 28%, respectively, when charcoal was administered at 2 and 6 h post-dose. Apixaban Cmax and Tmax were similar across treatments. The mean T½ for apixaban alone (13.4 h) decreased to ~5 h when activated charcoal was administered at 2 or 6 h post-dose. Overall, apixaban was well tolerated in this healthy population, and most adverse events were consistent with the known profile of activated charcoal.ConclusionAdministration of activated charcoal up to 6 h after apixaban reduced apixaban exposure and facilitated the elimination of apixaban. These results suggest that activated charcoal may be useful in the management of apixaban overdose or accidental ingestion.

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