MULTIPLE-DOSE ACTIVATED-CHARCOAL AND ENHANCEMENT OF SYSTEMIC DRUG CLEARANCE - SUMMARY OF STUDIES IN ANIMALS AND HUMAN VOLUNTEERS

Multiple-dose activated charcoal therapy can enhance the systemic elimination of many drugs. Studies in animals and human volunteers provide a framework for understanding the indications and limitations of multiple-dose activated charcoal therapy. Enterocapillary exsorption creates a compartment for diffusion of drugs out of the bloodstream and activated charcoal can augment this process to enhance drug clearance. Once charcoal reaches the intestine, there is a rapid onset of action. Clearance at exsorption sites is limited by blood flow, moreover, the rate of exsorption is related to the dose of charcoal up to a ceiling dose. Drug absorption, distribution, metabolism and elimination dynamically interact with multiple-dose activated charcoal therapy making it difficult to identify a single variable that may predict the success or failure with this therapy. Drug characteristics associated with enhanced systemic clearance with multiple-dose activated charcoal include a low intrinsic clearance, presence in the body for a sufficient time period for charcoal to act, a prolonged distributive phase, non-restrictive protein binding, and a small volume of distribution. Drugs that are unaffected at low doses may respond to multiple doses of activated charcoal when nonlinear kinetics are apparent due to overdose or disease. Although our current understanding is incomplete, multiple-dose activated charcoal therapy will play a role in the future therapy of poisoning patients.