Population pharmacokinetics of enfuvirtide in HIV-1-infected pediatric patients over 48 weeks of treatment.
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.
Zhang
Xiaoping
X
Hoffmann-La Roche, Inc, 340 Kingsland Street, Nutley, NJ 07110, USA. Xiaoping.zhang@roche.com
Lin
Tiffany
T
Bertasso
Anne
A
Evans
Claire
C
Dorr
Albert
A
Kolis
Stanley J
SJ
Salgo
Miklos
M
Patel
Indravadan
I
D000293:Adolescent; D000367:Age Factors; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000378:metabolism; D003710:Demography; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000097:blood / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044469:Racial Groups
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide; D003404:Creatinine