Effect of Activated Charcoal on Apixaban Pharmacokinetics in Healthy Subjects

• Published in: American journal of cardiovascular drugs : drugs, devices, and other interventions Vol. 14; no. 2; pp. 147 - 154
• Main Authors: Wang, Xiaoli, Mondal, Sabiha, Wang, Jessie, Tirucherai, Giridhar, Zhang, Donglu, Boyd, Rebecca A., Frost, Charles
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2014; Springer Nature B.V
• Subjects: Adolescent; Adult; Area Under Curve; Cardiology; Charcoal - adverse effects; Charcoal - pharmacology; Cross-Over Studies; Female; Fibrinolytic Agents - adverse effects; Fibrinolytic Agents - pharmacokinetics; Humans; Intestinal Absorption; Male; Medicine; Medicine & Public Health; Middle Aged; Original; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Pyrazoles - adverse effects; Pyrazoles - pharmacokinetics; Pyridones - adverse effects; Pyridones - pharmacokinetics; Rivaroxaban; Dabigatran; Activate Charcoal; Apixaban; Breast Cancer Resistance Protein
• ISSN: 1175-3277; 1179-187X
• DOI: 10.1007/s40256-013-0055-y

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 C max ( T max ), area under the concentration–time curve from time 0 to infinity (AUC INF ), and terminal half-life ( T ½ ), were derived from apixaban plasma concentration–time data. A general linear mixed-effect model analysis of C max and AUC INF was performed to estimate the effect of activated charcoal on apixaban exposure. Results A total of 18 subjects were treated and completed the study. AUC INF for apixaban without activated charcoal decreased by 50 and 28 %, respectively, when charcoal was administered at 2 and 6 h post-dose. Apixaban C max and T max were similar across treatments. The mean T ½ 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.