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Acetaminophen Does Not Impair Clearance of Zidovudine

Fred R. Sattler, MD; Richard Ko, PharmD; Diana Antoniskis, MD; Mark Shields, MS; Jordan Cohen, PhD; John Nicoloff; John Leedom; and Robert Koda, PharmD, PhD
[+] Article and Author Information

Grant Support: In part by contracts from the AIDS Clinical Trials Program of the National Institutes of Allergy and Infectious Diseases (NOI-AI-62540) and the California Collaborative Treatment Group of the State of California University-wide AIDS Research Program (RO-CC8650). Computational assistance was provided by the National Center for Research Resources of the General Clinical Research Centers CLINFO Project (MO1 RR-43).

Requests for Reprints: Fred R. Sattler, MD, Los Angeles County-University of Southern California Medical Center, 1175 North Cummings Street, 5P77N, Los Angeles, CA 90033.

Current Author Addresses: Drs. Sattler, Antoniskis, Nicoloflf, and Leedom: Los Angeles County-University of Southern California Medical Center, 1175 North Cummings Street, Los Angeles, CA 90033.

Dr. Ko: State of California Department of Health Services-FDB, 714 P. Street, Room 440, Sacramento, CA 95814.

Mr. Shields: University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033.

Dr. Cohen: College of Pharmacy, University of Kentucky, Rose Street, Pharmacy Building, Lexington, KY 40536.

Dr. Koda: University of Southern California School of Pharmacy, 1985 Zonal Avenue, Room 200C, Los Angeles, CA 90033.


©1991 American College of PhysiciansAmerican College of Physicians


Ann Intern Med. 1991;114(11):937-940. doi:10.7326/0003-4819-114-11-937
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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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