Effect of delayed administration of activated charcoal on the absorption of conventional and slow-release verapamil

Objective: To investigate the effect of simultaneous and delayed administration of activated charcoal on the absorption of two verapamil formulations. Methods: In the first study, 9 healthy volunteers received the following treatments: 1) verapamil 80 mg (conventional formulation) with 50 mL water only, 2) verapamil 80 mg and 25 g activated charcoal immediately afterwards, and 3) verapamil 80 mg with 50 mL water, followed by 25 g charcoal 2 h after verapamil ingestion. In the second study, 8 healthy volunteers received the following treatments: 1) verapamil 240 mg (slow-release formulation) with 50 mL water only, 2) verapamil slow-release 240 mg and 25 g activated charcoal immediately afterwards, 3) verapamil slow-release 240 mg with 50 mL water, followed by 25 g charcoal 2 h after verapamil ingestion, and 4) verapamil slow-release 240 mg with 50 mL water, followed by 25 g charcoal 4 h later. Plasma verapamil concentrations over 24 h were measured by high performance liquid chromatography. Results: Activated charcoal given immediately after the conventional formulation of verapamil reduced the AUC(0-24h) by 99% (p < 0.0005) and the C-max by 98% (p < 0.0005). When the administration of charcoal was delayed 2 h, no significant change in verapamil absorption was observed. With the slow-release formulation of verapamil, charcoal given immediately after verapamil ingestion reduced the verapamil AUC(0-24h) by 86% (p = 0.001) and the C-max by 82% (p = 0.002). When the administration of charcoal was delayed 2 or 4 h, the AUC(0-24h) was reduced by 35% (p = 0.04) and 32% (p = 0.001), respectively, but the C-max was decreased by 13% (p = NS) and 9% (p = NS) only. Conclusions: Activated charcoal was effective in preventing absorption of verapamil when it was administered immediately after verapamil ingestion. In the case of slow-release formulation, charcoal reduced verapamil absorption by over 30% even when given 4 h after verapamil.