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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

15 August 1997 | Volume 127 Issue 4 | Pages 289-293

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.

Author and Article 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.

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