Effect of activated charcoal on apixaban pharmacokinetics in healthy subjects

Abstract

Background: Activated 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. Methods: This 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 (C max), time to Cmax (Tmax), area under the concentration-time curve from time 0 to infinity (AUCINF), and terminal half-life (T1/2), were derived from apixaban plasma concentration-time data. A general linear mixed-effect model analysis of C max and AUCINF was performed to estimate the effect of activated charcoal on apixaban exposure. Results: A 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 T max were similar across treatments. The mean T 1/2 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. Conclusion: Administration 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. © 2013 The Author(s).