Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana

Background. We conducted a pharmacokinetic study of antimycobacterial drugs involving a cohort of patients with pulmonary tuberculosis (TB) in Gaborone, Botswana, to assess the prevalence of and risk factors for low drug concentrations in serum. Methods. Adults participated if they had a history of cough >= 2 weeks, had abnormal chest radiograph findings, consented to testing for human immunodeficiency virus (HIV), had sputum cultures positive for Mycobacterium tuberculosis, and were receiving antituberculous therapy for 17 days. Observed maximum serum concentrations were compared with published normal ranges. Results. Of 91 patients enrolled, 89 (98%) were outpatients, and 59 (68%) of 87 patients tested had HIV infection. The following numbers of patients had low serum concentrations of the following drugs: isoniazid, 27 (30%) of 90; rifampin, 71 (78%) of 91; ethambutol, 37 (41%) of 91; and pyrazinamide, 1 (1%) of 91. Low serum concentrations of both isoniazid and rifampin occurred in 23 (26%) of 90 patients. Low serum concentrations of rifampin were found in both HIV-infected and non-HIV-infected patients, and such patients were less likely to have 14 weeks of symptoms, more likely to have lymphadenopathy, and more likely to have low serum albumin levels ( for all). The associations with noncavitary pulmonary disease (P = .12) and HIV infection (P = .07) did not reach statistical significance. Delayed absorption was most common with ethambutol, followed by rifampin. Conclusions. These data, predominantly from HIV-infected patients with TB, suggest that low isoniazid, rifampin, and ethambutol concentrations are common in Botswana. In contrast, pyrazinamide usually is well absorbed.