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| Lack of a Pharmacokinetic Interaction between Emtricitabine and Tenofovir DF when Coadministered to Steady State in Healthy Volunteers |
| Category:
A1 |
M. R. BLUM, J. BEGLEY, J. ZONG, D. HILL, N. ADDA, G. CHITTICK;
Gilead Sciences, Inc., Durham, NC. |
| Presentation Number: A-1621 |
| Keywords:
FTC, tenofovir, interaction |
| Background: Emtricitabine (FTC) is a potent new NRTI in development for the treatment of HIV and HBV infection. As FTC will be combined with tenofovir DF (TDF) in once daily (QD) dosage regimens, a multiple-dose study was conducted to evaluate the potential for a pharmacokinetic (PK) interaction when these drugs are administered together at therapeutic doses. Methods: The study was a randomized, open-label, 3-period crossover design. During three 7-day dose periods, healthy male and female subjects received 200 mg FTC QD, 300 mg TDF QD or 200 mg FTC + 300 mg TDF QD, with no washout between periods. The last 3 doses of each treatment were taken shortly after a standard breakfast. A 24-hr PK evaluation was conducted following the last dose of each treatment, with FTC and tenofovir (TFV) plasma levels determined by a simultaneous LC/MS/MS method with lower limits of quantitation of 5 and 10 ng/mL, respectively. Analysis of variance was used for comparison of the PK parameters between treatments. PK analysis was conducted by standard non-compartmental methods. No interaction was concluded if the 90% confidence interval (CI) of the geometric least squares mean ratio (GLSMR) for steady-state AUC, Cmax and Cmin for drugs together vs. drugs alone were each within the range of 0.70 to 1.43, i.e., a maximum 30% effect. Results: Based on clinical and laboratory evaluations, FTC and TDF were well tolerated after multiple-dose administration alone and together. Two of 19 subjects enrolled discontinued the study; 1 for personal reasons and 1 for adverse events (multiple vomiting episodes on FTC + TDF). The GLSMR (CI) for FTC + TFV vs. FTC for AUC, Cmax, and Cmin were 1.06 (1.00-1.14), 0.96 (0.87-1.06), and 1.20 (1.12-1.29), respectively. The GLSMR (CI) for TFV + FTC vs. TFV for AUC, Cmax, and Cmin were 1.00 (0.92-1.09), 1.03 (0.95-1.11), and 1.02 (0.92-1.13), respectively. Conclusions: No PK interaction was observed when FTC and TDF are administered together. |
| Commercial Relationship: M.R. Blum, Gilead Sciences, Inc. F. |
| PresentationPreference: No Preference |
| NoOffLabel: True |
| GenericProductName: emtricitabine |
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