B Taylor1, P J Smith. 1. Department of Pharmacology, University of Cape Town Medical School, Observatory, Western Cape, South Africa.
Abstract
SETTING: Case reports of low serum concentrations of antituberculosis drugs, with resultant treatment failure and emergence of drug-resistant organisms in patients with the acquired immune-deficiency syndrome (AIDS), have prompted suggestions that therapeutic drug monitoring (TDM) may be indicated in patients co-infected with the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis. OBJECTIVE: To test whether the bioavailability of antituberculosis drugs is altered in HIV-infected patients with tuberculosis. METHOD: Twenty-seven hospitalized tuberculosis patients (13 with AIDS, 14 HIV-negative) were entered into a pharmacokinetic trial. Following the supervised administration of standardized doses of isoniazid, rifampicin and pyrazinamide, the plasma concentrations of the drugs were measured repeatedly over 12 hours and the following parameters were derived for each agent: maximum measured drug concentration (Cmax), time-to-maximum measured drug concentration (Tmax) and area-under-the-concentration-time curve to 12 hours (AUC). RESULTS: No significant differences emerged between the two groups in Cmax, Tmax, and AUC for isoniazid and pyrazinamide. For rifampicin the AIDS patients showed a greater AUC (P < 0.01) than the controls, but there were no significant differences in Cmax and Tmax. CONCLUSION: There was no evidence that HIV infection reduced the plasma concentrations of antituberculosis drugs.
SETTING: Case reports of low serum concentrations of antituberculosis drugs, with resultant treatment failure and emergence of drug-resistant organisms in patients with the acquired immune-deficiency syndrome (AIDS), have prompted suggestions that therapeutic drug monitoring (TDM) may be indicated in patients co-infected with the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis. OBJECTIVE: To test whether the bioavailability of antituberculosis drugs is altered in HIV-infectedpatients with tuberculosis. METHOD: Twenty-seven hospitalized tuberculosis patients (13 with AIDS, 14 HIV-negative) were entered into a pharmacokinetic trial. Following the supervised administration of standardized doses of isoniazid, rifampicin and pyrazinamide, the plasma concentrations of the drugs were measured repeatedly over 12 hours and the following parameters were derived for each agent: maximum measured drug concentration (Cmax), time-to-maximum measured drug concentration (Tmax) and area-under-the-concentration-time curve to 12 hours (AUC). RESULTS: No significant differences emerged between the two groups in Cmax, Tmax, and AUC for isoniazid and pyrazinamide. For rifampicin the AIDSpatients showed a greater AUC (P < 0.01) than the controls, but there were no significant differences in Cmax and Tmax. CONCLUSION: There was no evidence that HIV infection reduced the plasma concentrations of antituberculosis drugs.
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