title: Multiple-dose acetaminophen pharmacokinetics.
abstract: Four different treatments of acetaminophen (Tylenol) were administered in multiple doses to eight healthy volunteers. Each treatment (325, 650, 825, and 1000 mg) was administered five times at 6-h intervals. Saliva acetaminophen concentration versus time profiles were determined. Noncompartmental pharmacokinetic parameters were calculated and compared to determine whether acetaminophen exhibited linear or dose-dependent pharmacokinetics. For doses less than or equal to 18 mg/kg, area under the curve (AUC), half-life (t1/2), mean residence time (MRT), and ratio of AUC to dose for the first dose were compared with the last dose. No statistically significant differences were observed in dose-corrected AUC for the first or last dose among subjects or treatments. Half-lives and MRT were not significantly different among treatments for the first or the last dose. Statistically significant differences in t1/2 and MRT were noted (p less than 0.05) among subjects for the last dose. A plot of AUC versus dose for the first and the last doses exhibited a linear relationship. Dose-corrected saliva concentration versus time curves for the treatments were superimposable. Thus, acetaminophen exhibits linear pharmacokinetics for doses of 18 mg/kg or less. Plots of AUC versus dose for one subject who received doses higher than 18 mg/kg were curved, suggesting nonlinear behavior of acetaminophen in this subject.
authors.affiliation: College of Pharmacy, Oregon State University, Corvallis 97331-3507.
authors.forename: C G
authors.initials: CG
authors.lastname: Sahajwalla
authors.forename: J W
authors.initials: JW
authors.lastname: Ayres
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D006801:Humans
chemical_list: D000082:Acetaminophen