Temporal variations in acetaminophen and phenacetin half-life in man.
Acetaminophen (APAP) and phenacetin mean plasma half-lives were approximately 15% longer in normal male volunteers at 6 A.M. than at 2 P.M. as determined after oral administration of each drug at 6 A.M. and 2 P.M. Concentrations of plasma 11-hydroxycorticoids (11-OHCS) in these volunteers were approximately 42% higher at 6 A.M. than at 2 P.M. The mean apparent volume of distribution (aVd) of APAP decreased by approximately 13% from 6 A.M. to 2 P.M., whereas the mean metabolic clearance rate (MCR) of APAP did not change significantly. Neither the mean aVd nor the mean MCR of phenacetin changed significantly from 6 A.M. to 2 P.M. Measurement of urinary metabolites showed no alteration in APAP glucuronidation in the 8-hr period following APAP administration at 6 A.M. or 2 P.M., but indicated that after phenacetin administration 10% more of the dose was oxidatively metabolized to APAP during a 24-hr period beginning at 2 P.M. than at 6 A.M. Within each subject, plasma acetaminophen or phenacetin half-life at 2 P.M. or 6 A.M. was highly reproducible, but large interindividual variations occurred in the extent of temporal variation during this period.
D015062:11-Hydroxycorticosteroids / Q000097:blood; D000082:Acetaminophen / Q000097:blood* / Q000652:urine; D000328:Adult; D002986:Clinical Trials as Topic; D005965:Glucuronates / Q000652:urine; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D010084:Oxidation-Reduction; D010615:Phenacetin / Q000097:blood*; D013997:Time Factors
D015062:11-Hydroxycorticosteroids; D005965:Glucuronates; D000082:Acetaminophen; D010615:Phenacetin