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Temporal variations in acetaminophen and phenacetin half‐life in man
Author(s) -
Shively Carol A.,
Vesell Elliot S.
Publication year - 1975
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1975184413
Subject(s) - phenacetin , acetaminophen , medicine , anesthesia , pharmacology
Acetaminophen (AP AP) 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 (11‐0 HCS) 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 MC R 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 AP AP 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.