Effect of Delayed Administration of Activated Charcoal on the Absorption of Conventional and Slow-Release Verapamil

Abstract

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% by (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