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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
Abstract
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.
Article and Author Information
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From the University of Southern California and the Los Angeles County-University of Southern California Medical Center, Los Angeles, California. For current author addresses, see end of text.
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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).
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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.
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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 Physicians
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