Acute pharmacokinetics of first line anti-tuberculosis drugs in patients with Pulmonary Tuberculosis and in patients with Pulmonary Tuberculosis co-infected with HIV

Abstract

The aim of this study was to compare the pharmacokinetics of antituberculosis drugs in patients with pulmonary tuberculosis (PTB) and in patients with PTB and HIV during the first 24 h of treatment. Designed as a case-control study, it compares the pharmacokinetics of first line antituberculous drugs, in HIV-positive (cases) and HIV-negative (control) patients both presenting with pulmonary tuberculosis. Blood samples were collected before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 8, 12 and 24 h after administration of drugs. Drugs plasma levels were tested using HPLC assays. Results: Fourteen HIV positive (7 males and 7 females) and 17 HIV negative (9 males and 8 females) enrolled. Rifafour, a combination tablet including rifampicin, isoniazid, pyrazinamide and ethambutol was used in HIV positive patients, CD4 counts were significantly lower, renal function mildly decreased in 85% patients and moderately decreased in 7% patients. Liver function was normal in both groups. None of these patients was on other drug therapy. In the HIV positive group isoniazid T1/2 and AUC were decreased and Cl increased whereas Tmax and Cmax were unchanged. Pyrazinamide Tmax and Cmax were significantly decreased in HIV positive patients and no significant changes were noticed in the T1/2, AUC and CL. Conclusion: The study suggest that ethambutol, pyrazinamide and rifampicin pharmacokinetics was not affected by HIV infection and that isoniazid disposition is affected by HIV.