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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
- 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.
Abstract
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.
- Copyright ©2004 by the American College of Physicians
