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Pharmacokinetics (PK) and pharmacodynamics (PD) of enfuvirtide in HIV‐1‐infected children over 24 weeks of treatment
Author(s) -
Zhang X.,
Lin T.,
Dorr A.,
Bertasso A.,
Evans C.,
Rowell L.,
Kolis S.,
Veloso W.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.116
Subject(s) - enfuvirtide , medicine , pharmacokinetics , pharmacodynamics , pharmacology , viral load , regimen , metabolite , gastroenterology , human immunodeficiency virus (hiv) , gp41 , immunology , antibody , epitope
Background/Aims Enfuvirtide (ENF, Fuzeon®) is the first of a new class of HIV drugs (fusion inhibitors) that block gp41‐mediated viral fusion to host cells. The objective of this study was to measure sparse C trough levels of ENF and its major metabolite and to explore its pharmacodynamics (PD) in a group of HIV‐1‐infected children over 24 weeks of treatment. Methods 24 HIV‐1‐infected children (aged 5–11 years) who completed 24 weeks of a 48‐week multi‐center, open‐label, non‐randomized, non‐comparative treatment study were included in the analysis. Patients were dosed at 2 mg/kg (to a max dose of 90 mg) bid subcutaneously plus an optimized antiretroviral regimen. Plasma samples for determination of the C trough 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 cell counts were collected up to 24 weeks. Results Mean ENF C trough was 2.6 μg/mL at week 1 and 3.4 μg/mL at week 24. Mean ENF metabolite C trough was 0.17 μg/mL at week 1 and 0.41 μg/mL at week 24. Mean decline in plasma HIV‐1 RNA from baseline was −1.059 log 10 copies/mL at week 24. Mean increase in CD4 cell count from baseline was 190 cells/mm 3 at week 24. Mean CD8 cell count decreased from BL by 115 cells/mm 3 at week 24. Conclusions A dose of ENF at 2 mg/kg bid in a group of HIV‐1‐infected children achieved PK exposure which is stable over 24 weeks of treatment and comparable to that achieved in HIV‐1‐infected adolescents at the same dose and in adults at a dose of 90 mg bid. Clinical Pharmacology & Therapeutics (2005) 77 , P59–P59; doi: 10.1016/j.clpt.2004.12.116