Acetaminophen does not impair clearance of zidovudine.
OBJECTIVE
To determine whether concurrent treatment with acetaminophen and zidovudine impairs clearance of zidovudine, thereby increasing the risk for zidovudine-induced hematologic toxicity.


METHODS
Dose escalation, drug interaction study.


METHODS
University clinical research center.


METHODS
Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex.


METHODS
Acetaminophen and 200 mg of zidovudine simultaneously every 4 hours. For 13 patients, the unit dosage of acetaminophen was 325 mg for 3 days; for 8 patients, the dosage was 650 mg for 3 days; and, for 6 patients, the dosage was 650 mg for 7 days.


METHODS
Zidovudine clearance and production of the glucuronide conjugate of zidovudine were assessed after acetaminophen treatment.


RESULTS
Neither zidovudine clearance nor production of the glucuronide conjugate of zidovudine was impaired after treatment with acetaminophen. Clearance of zidovudine was actually accelerated by 5%, 11%, and 33% with the three acetaminophen regimens, respectively (P = 0.002 by analysis of variance; P = 0.04 for linear trend when changes in the area-under-the-curve for zidovudine were compared).


CONCLUSIONS
Because serum concentrations of zidovudine decrease after the coadministration of acetaminophen, a pharmacokinetic interaction between zidovudine and acetaminophen is unlikely to increase the risk for hematologic toxicity associated with zidovudine.
Sattler
F R
FR
University of Southern California, Los Angeles.
Ko
R
R
Antoniskis
D
D
Shields
M
M
Cohen
J
J
Nicoloff
J
J
Leedom
J
J
Koda
R
R
D000386:AIDS-Related Complex / Q000188:drug therapy; D000082:Acetaminophen / Q000494:pharmacology*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000328:Adult; D000704:Analysis of Variance; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics*
D000082:Acetaminophen; D015215:Zidovudine