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| A Steady-state Evaluation of the Potential Pharmacokinetic Interaction between Emtricitabine and Zidovudine in Healthy Volunteers |
| Category:
A1 |
J. ZONG, M. R. BLUM, G. CHITTICK, R. HART, M. BROSNAN-COOK, N. ADDA;
Gilead Sciences, Inc., Durham, NC. |
| Presentation Number: A-1620 |
| Keywords:
emtricitabine, interaction, AZT |
| Background: Emtricitabine (FTC) is a new NRTI in development with potent activity against HIV and HBV. A multiple-dose study was conducted to evaluate the potential for a pharmacokinetic (PK) interaction between FTC and zidovudine (ZDV) when administered together at therapeutic doses. Methods: The study was of randomized, open-label, 3-period crossover design. During three 7-day dose periods, 30 healthy male and female subjects received 200 mg FTC QD, 300 mg ZDV BID or 200 mg FTC QD + 300 mg ZDV BID, with no washout between periods. A 24-hr PK evaluation was conducted following the last dose of each treatment, with plasma levels of FTC, ZDV and ZDV-glucuronide (GZDV) determined simultaneously by a LC/MS/MS method with lower limits of quantitation of 5 ng/mL for FTC and ZDV and 20 ng/mL for GZDV. PK analysis was conducted by standard noncompartmental methods. Analysis of variance was used for comparison of the PK parameters between the different treatment. 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. drug 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 ZDV were generally well tolerated after multiple-dose administration alone or together. Three subjects discontinued the study; 2 for adverse events (severe diarrhea and moderate nausea, respectively, both on ZDV alone) and 1 who was unevaluable for the PK evaluation. The GLSMR (CI) for FTC + ZDV vs. FTC for AUC, Cmax, and Cmin were 0.97 (0.93-1.01), 0.97 (0.90-1.04), and 0.96 (0.88-1.04), respectively. The GLSMR (CI) for ZDV + FTC vs. ZDV for AUC, Cmax, and Cmin were 1.13 (1.05-1.20), 1.17 (1.00-1.38), and 0.98 (0.89-1.09), respectively. The results for GZDV paralleled those for ZDV. Conclusions: No PK interaction was observed when FTC and ZDV were administered together. |
| Commercial Relationship: J. Zong, Gilead Sciences, Inc. F. |
| PresentationPreference: No Preference |
| NoOffLabel: True |
| GenericProductName: emtricitabine |
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