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Population Pharmacokinetics of Enfuvirtide in HIV‐1‐Infected Pediatric Patients Over 48 Weeks of Treatment
Author(s) -
Zhang Xiaoping,
Lin Tiffany,
Bertasso Anne,
Evans Claire,
Dorr Albert,
Kolis Stanley J.,
Salgo Miklos,
Patel Indravadan
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006299089
Subject(s) - enfuvirtide , pharmacokinetics , nonmem , medicine , population , dosing , trough concentration , human immunodeficiency virus (hiv) , pharmacology , gastroenterology , virology , immunology , environmental health , antigen , gp41 , epitope
The objective of this study was to characterize the population pharmacokinetics of enfuvirtide in HIV‐1‐infected children and adolescents. HIV‐infected patients received combination antiretroviral therapy, including enfuvirtide 2.0 mg/kg subcutaneously, twice daily. Serial and trough blood samples were collected up to 48 weeks. NONMEM was used for population pharmacokinetic analysis. Enfuvirtide exposure was calculated from individual parameter estimates derived from the final model. A total of 218 samples from 43 patients were included in the analysis. Enfuvirtide plasma concentration–time data were described by a 1‐compartment model with first‐order absorption and elimination. The addition of each subject's actual body weight as a covariate affected CL/F but not V/F or K a . The population CL/F, V/F, and K a for a 33‐kg reference patient was 1.31 L/h, 2.31 L, and 0.105 h −1 , respectively. The final model was CL/F (L/h) = 1.31 · (body weight/33 [kg]) 0.721 . Age did not affect enfuvirtide exposure. These results confirm the appropriateness of body weight–based pediatric enfuvirtide dosing.