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Background:  Stavudine extended-release formulation (D4T XR) and tenofovir disoproxil fumarate (TDF) are potential components of once-daily HAART regimens. In the present investigation, we report the effect of D4T XR and TDF co-administration on the pharmacokinetics of tenofovir in healthy subjects.

Methods:  In a single-center, open-label study, 18 healthy subjects completed the following protocol. Day 1:  subjects received a single oral dose of 100 mg D4T XR with a light meal (373 kcal). Days 2-8:  subjects received oral, once-daily 300 mg TDF with a light meal. Day 9:  subjects received a single oral dose of 100 mg D4T XR with 300 mg of TDF and a light meal. Serial blood samples were collected at selected times over a 24-hour period on days 1, 8, and 9 for pharmacokinetic assessments of tenofovir. Serum concentrations of tenofovir were determined by a validated LC/MS/MS analytical method, and the resulting concentration-time data were subjected to a non-compartmental pharmacokinetic analysis. Clinical safety evaluations, including clinical laboratory tests, were performed at screening, during, and prior to discharge from the study. 

Results:  Serum tenofovir concentration-versus time profile for the D4T XR+TDF treatment was superimposable on the profile for the TDF alone treatment. The geometric mean (%CV) for Cmax and AUC, and median Tmax values for tenofovir were 320 ng/mL (20%), 3048 ng.h/mL (20%), and 2.0 h, respectively, for the TDF alone treatment; the corresponding values for the D4T XR+TDF treatment were 333 ng/mL (17%), 3032 ng.h/mL (16%), and 1.5 h, respectively. There were no serious adverse events or discontinuations due to AEs. The most frequently reported treatment-emergent adverse events were nausea, body ache, and fatigue (2 subjects each).

Conclusions:  D4T XR did not influence the pharmacokinetics of tenofovir and no dose modification is required when TDF is coadministered with D4T XR.

Keywords: Stavudine; Tenofovir; Drug-interaction