A study of pharmacokinetics of anti tuberculosis drugs in Zambian PTB patients co-infected with the Human Immuno-Deficiency Virus

Abstract

The present study assesses the pharmacokinetic parameters for rifampicin, isoniazid and pyrazinamide in Zambian PTB patients with HIV at the University Teaching Hospital, Lusaka, Zambia. The assaying of the drugs was done at the University College London Medical School.To determine whether the pharmacokinetics of anti-tuberculosis drugs at steady-state are altered in HIV infected patients especially those with chronic diarrhoea.60 pulmonary tuberculosis patients, (20 HIV negative, 20 HIV positive without diarrhoea and 20 HIV positive patients with diarrhoea) were entered into a pharmacokinetic trial. Following supervised administration of standard doses of isoniazid, rifampicin and pyrazinamide, the plasma concentrations were measured over 24 hours to obtain the pharmacological parameters of the drugs. The following were then compared in the three groups for any significant difference: maximum measured drug concentration (Cmax) and area-under-the-concentration-time curve to 24 hours (AUC).No notable differences emanated between the three groups i.e. HIV negative, HIV positive without and with chronic diarrhoea, on comparing the Cmax and AUC (P>0.05). 20% of the participants were found to be fast acetylators (extrapolated using tl/2 for isoniazid).This study could find no conclusive evidence that HIV infection, especially associated chronic diarrhoea affected the pharmacokinetics of the anti-tuberculosis drugs.