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Reduced Plasma Concentrations of Antituberculosis Drugs in Patients with HIV Infection

Jan Sahai, PharmD; Keith Gallicano, PhD; Lori Swick, BSc; Sandra Tailor, PharmD; Gary Garber, MD; Isabelle Seguin, RN; Linda Oliveras, MLT; Scott Walker, MSc; Anita Rachlis, MD; and D. William Cameron, MD
[+] Article and Author Information

From the University of Ottawa at the Ottawa General Hospital and Health Canada, Ottawa, Ontario, Canada; and Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Acknowledgments: The authors thank Attila Pakuts (Health Canada) and Nicole Lee (Ottawa General Hospital) for technical assistance and Eric Ormsby and Bob Li (Health Canada) for statistical advice. Grant Support: In part by the Burroughs Wellcome Positive Action Program, administered by the Ontario Ministry of Health, Ontario, Canada. Dr. Cameron is a Career Scientist of the Ontario Ministry of Health (award #02984). Requests for Reprints: Keith Gallicano, PhD, Clinical Investigation Unit, Ottawa General Hospital, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. Current Author Addresses: Dr. Sahai: Hoffmann-La Roche, Pharmaceutical Division, BioMed Business Unit, 2455 Medowpine Boulevard, Mississauga, Ontario L5N 6L7, Canada.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;127(4):289-293. doi:10.7326/0003-4819-127-4-199708150-00006
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Background: Reports suggest that antituberculosis drugs are malabsorbed in patients with advanced HIV disease.

Objective: To evaluate the pharmacokinetics of antituberculosis agents in HIV-seropositive patients at different stages of disease.

Design: Parallel study.

Setting: Two hospital outpatient clinics.

Participants: 12 healthy volunteers, 12 patients with asymptomatic HIV disease, 12 patients with symptomatic HIV disease, and 12 patients with symptomatic HIV disease and diarrhea.

Measurements: Drug plasma concentrations were measured over 24 hours on day 4 of concurrent therapy.

Intervention: Oral isoniazid (300 mg/d), rifampin (600 mg/d), pyrazinamide (1000 mg/d), and ethambutol (1000 mg/d).

Results: Reduced total drug exposure to rifampin and pyrazinamide was associated with D-xylose malabsorption in persons with HIV infection or AIDS. Peak drug exposure to isoniazid was lower in patients with diarrhea.

Conclusions: Reduced total drug exposure may be related to malabsorption in persons with HIV infection or AIDS.

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