Fred R. Sattler, MD; Richard Ko, PharmD; Diana Antoniskis, MD; Mark Shields, MS; Jordan Cohen, PhD; John Nicoloff; John Leedom; Robert Koda, PharmD, PhD
Objective: To determine whether concurrent treatment with acetaminophen and zidovudine impairs clearance of zidovudine, thereby increasing the risk for zidovudine-induced hematologic toxicity.
Design: Dose escalation, drug interaction study.
Setting: University clinical research center.
Patients: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex.
Interventions: 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.
Measurements: Zidovudine clearance and production of the glucuronide conjugate of zidovudine were assessed after acetaminophen treatment.
Main 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).
Conclusion: 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.
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Sattler FR, Ko R, Antoniskis D, Shields M, Cohen J, Nicoloff J, et al. Acetaminophen Does Not Impair Clearance of Zidovudine. Ann Intern Med. 1991;114:937-940. doi: 10.7326/0003-4819-114-11-937
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Published: Ann Intern Med. 1991;114(11):937-940.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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