Pharmacokinetics (PK) and pharmacodynamics (PD) of enfuvirtide in hiv-1 infected adolescents over 24 weeks of treatment

Abstract

Objective Enfuvirtide (ENF, T‐20, Fuzeon®) is the first of a novel class of HIV drugs which block gp41‐mediated viral fusion to host cells and has been recently approved by both the FDA and European Union. The objective of this study was to evaluate time stability of the pharmacokinetics (PK) of ENF and its metabolite and its antiretroviral activity (PD) in a group of HIV‐1 infected adolescents. Methods Twenty‐eight HIV‐1 infected adolescents (aged 12‐17 years) who completed 24 weeks of a 48–week treatment study were included in the analysis. These patients were dosed subcutaneously with ENF dose of 2 mg/kg (to a maximum dose of 90 mg) b.i.d. subcutaneously in combination with an optimized antiretroviral regimen. Plasma samples for determination of the Ctrough of ENF and its metabolite were collected at 12±2 hr post‐dose at various weeks. Blood samples for determination of HIV‐1 RNA viral load and CD4+ and CD8+ T cell count were collected up to 24 weeks. Results Mean ENF Ctrough was 3.2 μg/mL at week 1 and 2.4 μg/mL at week 24. Mean ENF Ctrough was stable over 24 weeks of treatment. Mean ENF metabolite Ctrough was stable from week 1 (0.29 μg/mL) to week 24 (0.22 μg/mL). Decline in plasma HIV‐1 RNA from baseline (5.19 log10 copies/mL) was −0.974 log10 copies/mL at week 24. The increase in CD4+ count from baseline (131 cells/mm3) was 148 cells/mm3 at week 24. The increase in CD8+ count from baseline (626 cells/mm3) was 398 cells/mm3 at week 24. Conclusion Dose of 2 mg/kg b.i.d. to a group of HIV‐1 infected adolescents achieved PK exposure which is stable over 24 weeks of treatment and comparable to that achieved in adults at 90 mg b.i.d. dose. Clinical Pharmacology & Therapeutics (2004) 75, P26–P26; doi:

Population Pharmacokinetics of Enfuvirtide in HIV‐1‐Infected Pediatric Patients Over 48 Weeks of Treatment

“…6 The enfuvirtide C trough values were also shown to be stable over 24 weeks of treatment. 7,8 The objective of the present analysis was to characterize the population pharmacokinetics of enfuvirtide and to investigate the effect of demographic factors on its pharmacokinetic variability in the overall cohort of HIV-1-infected pediatric patients in study T20-310/NV16056 over 48 weeks of treatment. This analysis was also planned to address whether the body weight-based dosing in the current dosing guidelines is justified.…”