Correlation of drug pharmacokinetics and effectiveness of multiple-dose activated charcoal therapy.
OBJECTIVE
To evaluate an animal model of multiple-dose activated charcoal (MDAC) therapy and correlate the pharmacokinetic properties of four drugs with the efficacy of MDAC.


METHODS
Prospective, randomized, controlled, crossover design.


METHODS
A university animal research facility.


METHODS
Seven female pigs (15 to 22 kg) with an indwelling central venous line and gastrostomy tube.


METHODS
Acetaminophen (30 mg/kg), digoxin (30 micrograms/kg), theophylline (8.9 mg/kg), and valproic acid (18 mg/kg) were simultaneously administered intravenously over 12 minutes. In the experimental arm, 25 g activated charcoal was administered at 0, 2, 4, 6, 12, 18, 24, and 30 hours through the gastric tube. In the control arm, an equal volume of water was given at the same times. Blood specimens were obtained over 36 hours to measure serum drug concentrations.


RESULTS
Each drug exhibited enhanced elimination (P < .01) in the MDAC group except valproic acid. Lower intrinsic clearance was correlated (P < .05) with increased systemic elimination during the charcoal arm. Volume of distribution, half-life, and protein binding were not significantly correlated with charcoal-enhanced systemic drug elimination.


CONCLUSIONS
The response of a drug to MDAC may be affected by its intrinsic clearance. The restrictive nature of the protein binding of valproic acid may be responsible for its lack of response. Results with the porcine model are consistent with the effects observed in human beings.
Chyka
P A
PA
Department of Clinical Pharmacy, University of Tennessee, Memphis.
Holley
J E
JE
Mandrell
T D
TD
Sugathan
P
P
D000082:Acetaminophen / Q000493:pharmacokinetics; D000818:Animals; D002606:Charcoal / Q000008:administration & dosage*; D004077:Digoxin / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D016014:Linear Models; D008657:Metabolic Clearance Rate; D010599:Pharmacokinetics; D011041:Poisoning / Q000188:drug therapy*; D011042:Poisons; D011446:Prospective Studies; D011897:Random Allocation; D013552:Swine; D013806:Theophylline / Q000493:pharmacokinetics; D014635:Valproic Acid / Q000493:pharmacokinetics
D011042:Poisons; D002606:Charcoal; D000082:Acetaminophen; D014635:Valproic Acid; D004077:Digoxin; D013806:Theophylline