Background: A once daily formulation of stavudine (d4T XR) was developed to simplify HIV treatment. This study was designed to investigate the effect of d4T XR and Tenofovir Disoproxil Fumarate (TDF) co-administration on the pharmacokinetics of d4T XR and TDF in healthy subjects.

Methods: In a single-center, open-label study, 18 healthy subjects completed the following protocol. Day 1: subjects received a single 100 mg oral dose of d4T XR with a light meal (373 kcal). Days 2–8: subjects received once-daily 300 mg oral dose of TDF with a light meal (373 kcal). Day 9: subjects received a single 100 mg oral dose of d4T XR with 300 mg of TDF and a light meal (373 kcal). Serial blood and urine samples were collected at selected times over a 24-hr period on days 1, 8, and 9 for PK assessments. Plasma concentrations of d4T were determined by a validated LC/MS/MS analytical method, and the resulting concentration-time data were subjected to a non-compartmental PK analysis. D4T urine and TDF serum and urine assays are currently ongoing. Clinical safety evaluations, including clinical laboratory tests, were performed at screening, during, and prior to discharge from the study.

Results: Plasma d4T concentration-versus time profile for the d4T XR+TDF treatment was super-imposable on the profile for the d4T XR alone treatment. The geometric mean (%CV) for Cmax and AUC, and median Tmax values were 274 (31%) ng/mL, 2,682 (29%) ng.h/mL, and 5 h, respectively, for the d4T XR alone treatment; the corresponding values for the d4T XR+TDF treatment were 275 (26%) ng/mL, 2,765 (28%), and 4 h, respectively. There were no serious adverse events (AEs) or discontinuations due to AEs. The most frequently reported treatment-emergent AEs were nausea, body ache, and fatigue (2 subjects each).

Conclusions: TDF did not influence the PK of d4T XR. D4T XR does not require dose modification when co-administered with TDF.