Decreased bioavailability of rifampicin and other anti-tb drugs in patients with advanced HIV disease

Abstract

Background Malabsorption of drugs from the gastro-intestinal tract due to HIV enteropathy and concurrent infections could lower the bioavailability of anti-tuberculosis (TB) drugs in HIV infected individuals. Our aim was to study the pharmacokinetics of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) in HIV infected Indian subjects. The D-xylose absorption test was also performed in all the patients. Method We studied 13 patients with smear positive pulmonary TB, 13 with HIV & diarrhoea and 14 with HIV & TB. Rifampicin (450mg), INH (600mg), PZA (1500mg) and EMB (1200mg) were administered orally. The plasma levels of RMP and INH at different time points and urinary levels of all drugs/metabolites were estimated. Results A significant decrease in peak concentrations of RMP in HIV & diarrhoea and HIV & TB patients was observed when compared to patients with TB, the values being 3.23, 3.27 & 8.27μg/ml respectively (P<0.001). Significant decrease in AUC of RMP was also observed in HIV patients. The bioavailability of INH was reduced in rapid acetylators in HIV patients with and without TB. The urinary excretion of all four drugs/metabolites and D-xylose was reduced in both HIV groups of patients. Conclusion Patients with HIV & TB and/or diarrhoea have decreased bioavailability of first line anti-TB drugs. This could have implications for TB treatment of HIV infected patients. Clinical Pharmacology & Therapeutics (2004) 75, P29–P29; doi: 10.1016/j.clpt.2003.11.108