PHARMACOKINETICS OF ANTIMYCOBACTERIAL DRUGS IN PATIENTS WITH TUBERCULOSIS, AIDS, AND DIARRHEA

To test the hypothesis that antituberculous drug disposition is altere d in patients with AIDS, we studied the steady-state pharmacokinetics of isoniazid (300 mg/d), rifampin (600 mg/d), and pyrazinamide (1,500 mg/d) in 29 adults (14 patients infected with human immunodeficiency v irus [HIV] and 15 non-HIV-infected patients) with tuberculosis in Nair obi, Kenya. Intestinal integrity was assessed with xylose, Neither HIV infection nor diarrhea accounted for the interpatient variability in the area-under-the-plasma concentration vs. time curve (AUG), the maxi mum concentration, or the terminal half-life (tia) of isoniazid, rifam pin, and pyrazinamide, No significant association between HIV infectio n or diarrhea and pharmacokinetics was seen for any of the compounds, In addition, neither the AUC nor the t(1/2) of any of these drugs refl ected interpatient differences in CD4 lymphocyte counts, Xylose absorp tion was uniformly low, We did not demonstrate that HIV infection, dia rrhea, or CD4 lymphocyte counts contributed significantly to the varia bility in pharmacokinetics of isoniazid, rifampin, and pyrazinamide in TB patients in Nairobi.