Pharmacokinetics of rifabutin during atazanavir/ritonavir co-administration in HIV-infected TB patients in India

Abstract

Setting: Rifabutin (RBT) is reported to be as effective as and to have less inducing effect on cytochrome P450 enzymes than rifampicin against tuberculosis (TB). The optimal dose of RBT during ritonavir (RTV) co-administration remains a matter of debate. Objective: To study the pharmacokinetics of 150 mg RBT thrice weekly during concomitant atazanavir/RTV administration in human immunodeficiency virus (HIV) infected TB patients. Methods: This observational study was conducted in 16 adult HIV-infected TB patients being treated for TB with an RBT-containing regimen and an antiretroviral therapy regimen with RTV; the dose of RBT was 150 mg thrice weekly. Serial blood draws were performed at pre-dosing and at 1, 2, 4, 6, 8, 12 and 24 h after the drug was administered. Plasma RBT was estimated using high-performance liquid chromatography. Results and Conclusions: Peak RBT concentration was below the lower therapeutic limit (<0.3 μg/ml) in seven patients, while 10 patients had trough concentrations below the minimal inhibitory concentration against Mycobacterium tuberculosis (0.06 μg/ml), suggesting that the RBT dosage may be inadequate. Prospective studies in different settings are required to arrive at the proper therapeutic dose for RBT to be used during co-administration with RTV.