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Pharmacokinetics (PK) and pharmacodynamics (PD) of enfuvirtide in hiv‐1 infected adolescents over 24 weeks of treatment
Author(s) -
Zhang X.,
Dorr A.,
Siddique Z.,
Bertasso A.,
Rowell L.,
Kolis S.
Publication year - 2004
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.2003.11.099
Subject(s) - enfuvirtide , pharmacodynamics , pharmacokinetics , pharmacology , human immunodeficiency virus (hiv) , medicine , antiretroviral therapy , virology , viral load , immunology , antibody , gp41 , epitope
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 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 + T cell count were collected up to 24 weeks. Results Mean ENF C trough was 3.2 μg/mL at week 1 and 2.4 μg/mL at week 24. Mean ENF C trough was stable over 24 weeks of treatment. Mean ENF metabolite C trough 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 log 10 copies/mL) was −0.974 log10 copies/mL at week 24. The increase in CD4 + count from baseline (131 cells/mm3) was 148 cells/mm 3 at week 24. The increase in CD8 + count from baseline (626 cells/mm 3 ) was 398 cells/mm 3 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: 10.1016/j.clpt.2003.11.099