Constraints on the enhancement of elimination of drugs with activated charcoal.
Both extracorporeal hemoperfusion through charcoal-containing columns and repeated oral administration of charcoal can accelerate clearance of some drugs or toxins from the systemic circulation. The efficacy of these 2 interventions is limited by a variety of factors, and the complex kinetic equations describing charcoal-induced clearance provide little practical clinical guidance about the potential efficacy of charcoal in accelerating clearance of a specific drug or toxin without previous empiric data. We derive here simple rules that place an upper limit on the maximal fraction of an absorbed dose of drug that can be removed (FRmax) by charcoal in terms of the volume of distribution (Vd), a parameter which is known for most drugs. For 4 h of hemoperfusion, a theoretical upper limit of FRmax is (1/Vd), where Vd is expressed in L/kg of body weight, and actual fractional removal (FR) will not exceed [1/(2 x Vd)]. Drug removal by 24 h of repeated po administration of charcoal exhibits similar relationships between FRmax and Vd, when charcoal-induced clearance derives primarily from removal of drug from blood perfusing in gastrointestinal mucosa. These relationships offer a simple means to evaluate the potential efficacy of acceleration of drug clearance by activated charcoal for drugs with a known value for Vd, and the relationships indicate that such interventions are impractical for drugs with very large values for Vd, such as tricyclic antidepressants.
Turk
J
J
Department of Medicine, Washington University School of Medicine, St Louis, MO.
Aks
S E
SE
Hryhorczuk
D O
DO
D000042:Absorption; D002606:Charcoal / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006464:Hemoperfusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D013806:Theophylline / Q000493:pharmacokinetics* / Q000506:poisoning
D002606:Charcoal; D013806:Theophylline