Correlation of Drug Pharmacokinetics and Effectiveness of Multiple-Dose Activated Charcoal Therapy

Peter Chyka, Joseph E. Holley, Timothy D. Mandrell, Prasanna Sugathan

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Study 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. Design: Prospective, randomized, controlled, crossover design. Setting: A university animal research facility. Participants: Seven female pigs (15 to 22 kg) with an indwelling central venous line and gastrostomy tube. Interventions: Acetaminophen (30 mg/kg), digoxin (30 μg/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. Conclusion: 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 PA, Holley JE, Mandrell TD, Sugathan P: Correlation of drug pharmacokinetics and effectiveness of multiple-dose activated charcoal therapy. Ann Emerg Med March 1995;25:356-362.].

Original languageEnglish (US)
Pages (from-to)356-362
Number of pages7
JournalAnnals of Emergency Medicine
Volume25
Issue number3
DOIs
StatePublished - Jan 1 1995

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Charcoal
Pharmacokinetics
Pharmaceutical Preparations
Valproic Acid
Therapeutics
Protein Binding
Swine
Gastrostomy
Digoxin
Theophylline
Acetaminophen
Cross-Over Studies
Half-Life
Stomach
Animal Models
Water
Serum

All Science Journal Classification (ASJC) codes

  • Emergency Medicine

Cite this

Correlation of Drug Pharmacokinetics and Effectiveness of Multiple-Dose Activated Charcoal Therapy. / Chyka, Peter; Holley, Joseph E.; Mandrell, Timothy D.; Sugathan, Prasanna.

In: Annals of Emergency Medicine, Vol. 25, No. 3, 01.01.1995, p. 356-362.

Research output: Contribution to journalArticle

Chyka, Peter ; Holley, Joseph E. ; Mandrell, Timothy D. ; Sugathan, Prasanna. / Correlation of Drug Pharmacokinetics and Effectiveness of Multiple-Dose Activated Charcoal Therapy. In: Annals of Emergency Medicine. 1995 ; Vol. 25, No. 3. pp. 356-362.
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