Dose-dependent adsorptive capacity of activated charcoal for gastrointestinal decontamination of a simulated paracetamol overdose in human volunteers.
The amount of activated charcoal needed to treat drug overdoses has arbitrarily been set at a charcoal-drug ratio of 10:1. Recent in vitro studies have shown a larger adsorptive capacity for activated charcoal when used in a model of paracetamol overdose. In the present study, we investigated whether this reserve capacity exists in vivo. This is clinically relevant in cases of large overdoses or if the full standard dose of 50 g activated charcoal cannot be administered. We performed a randomized, cross-over study (n = 16). One hour after a standard breakfast, 50 mg/kg paracetamol was administered, followed 1 hr later by an activated charcoal-Water slurry containing 50 (control), 25 or 5 g activated charcoal. The areas under the serum concentration-time curve (AUC) for paracetamol were used to estimate the efficacy of each activated charcoal dose. The AUC of the 25-g dose was found to be of similar size compared to the control, although statistics were weak. The AUC of the 5-g dose was 59% larger than the AUC of the 50-g dose (p = 0.0003). The terminal elimination half-life (t(1/2)) of paracetamol was 1.6 (CI 1.4-2.0) and 1.9 (CI 1.5-2.4) hr for 50 and 25 g, respectively (NS), and 2.5 (CI 1.8-3.0) hr for the 5-g dose (p = 0.003). The decrease in t(1/2) of paracetamol for the two larger activated charcoal doses indicates a possible effect of activated charcoal on paracetamol clearance and warrants further investigation. The large adsorptive reserve capacity of activated charcoal in vitro could not be reproduced for the smallest dose of activated charcoal. An activated charcoal-drug ratio of 10:1 is therefore still recommendable.
Gude
Anne-Bolette Jill
AB
Department of Clinical Pharmacology, Bispebjerg University Hospital, Copenhagen, Denmark.
Hoegberg
Lotte Christine Groth
LC
Angelo
Helle Riis
HR
Christensen
Hanne Rolighed
HR
D000042:Absorption; D000082:Acetaminophen / Q000493:pharmacokinetics / Q000506:poisoning*; D000327:Adsorption; D000328:Adult; D000931:Antidotes / Q000627:therapeutic use*; D002606:Charcoal / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose / Q000628:therapy; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D008297:Male
D000931:Antidotes; D002606:Charcoal; D000082:Acetaminophen