Pharmacokinetic Study of Tenofovir Disoproxil Fumarate Combined with Rifampin in Healthy Volunteers

Abstract

Tenofovir disoproxil fumarate (tenofovir DF) was studied in combination with rifampin in 24 healthy subjects in a multiple-dose, open-label, single-group, two-period study. All subjects were given tenofovir DF at 300 mg once a day (QD) from days 1 to 10 (period 1). From days 11 to 20 the subjects received tenofovir DF at 300 mg combined with rifampin at 600 mg QD (period 2). The multiple-dose pharmacokinetics of tenofovir (day 10 and 20) and rifampin (day 20) were assessed. The drug-related adverse events (AEs) experienced during this study were mostly mild. Only one grade 3 AE possibly or probably related to the treatment (raised liver enzyme levels) occurred during period 2; the subject was withdrawn from the study. Pharmacokinetic data for 23 subjects were thus evaluable. Point estimates for the mean ratios of tenofovir with rifampin versus tenofovir alone for the area under the concentration-time curve from time zero to 24 h (AUC 0-24 ), the maximum concentration of drug in plasma (C max ), and the minimum concentration of drug in plasma (C min ) were 0.88, 0.84, and 0.85, respectively. The 90% classical confidence intervals for AUC 0-24 , C max , and C min were 0.84 to 0.92, 0.78 to 0.90, and 0.80 to 0.91, respectively, thus suggesting pharmacokinetic equivalence. Similarly, coadministration of rifampin and tenofovir DF did not result in changes in the values of the tenofovir pharmacokinetic parameters. For rifampin, the values of the pharmacokinetic parameters found in this study were comparable to those found in the literature, indicating that tenofovir DF has no effect on the pharmacokinetics of rifampin. In conclusion, adaptation of either the rifampin or the tenofovir DF dose for the simultaneous treatment of tuberculosis and human immunodeficiency virus (HIV) infection in HIV-infected patients is probably not required.

Lack of a Significant Drug Interaction between Raltegravir and Tenofovir

“…There was no meaningful effect on tenofovir C 24 . The effect of raltegravir on tenofovir is similar in magnitude to the reported slight decrease in tenofovir PK parameter values observed on codosing of rifampin with TDF (4). No dose adjustment is recommended for TDF when it is coadministered with rifampin (Viread [tenofovir disoproxil fumarate] package insert, 2007 update), which implies that the observed effect of raltegravir on TDF is also of no clinical significance.…”

Dysregulation of Endoplasmic Reticulum Stress and Autophagic Responses by the Antiretroviral Drug Efavirenz

“…Cells were exposed to the following combinations of ARVds: cART1 (10 mM efavirenz, 5 mM emtricitabine, and 1 mM tenofovir) or cART2 (1 mM atazanavir, 60 nM ritonavir, 5 mM emtricitabine, and 1 mM tenofovir) in serum-free and antibioticfree EBM-2 basal media. These concentrations reflect the physiologic level of the drugs (Marzolini et al, 2001;Stahle et al, 2004;Droste et al, 2005;Boffito et al, 2011;Valade et al, 2014). For example, successful therapy was observed in patients with plasma concentrations of efavirenz between 1000 and 4000 mg/l, which translates to 3.17 and 12.67 mM.…”

Determination of Plasma Tenofovir Concentrations Using a Conventional LC-MS Method

“…These results indicate our newly developed method achieves a high degree of reproducibility and accuracy. As plasma concentrations of tenofovir are expected in the 0.05 to 0.40 mg/ml range when tenofovir is administered at the recommended dose, 4,17) our method successfully covers this region with good precision and accuracy. Actually, plasma tenofovir concentrations after oral administration of 300 mg to an HIV-1-infected patient were in this range.…”

“…These concentrations were similar to those reported previously. 11,12,17) DISCUSSION Prior to this study we tried to determine tenofovir plasma concentrations using a previously described HPLC method.…”