title: Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects.
abstract: OBJECTIVE
  Tesamorelin is a synthetic analogue of growth hormone-releasing factor (GRF), which increases basal and pulsatile growth hormone (GH) secretion and subsequently increases insulin-like growth factor (IGF)-1. Limited information is available about the pharmacokinetics of this compound. Consequently, the aim of this study was to characterize the population pharmacokinetics of tesamorelin in HIV-infected patients and healthy subjects.
  
  
  METHODS
  A total of 38 HIV-infected patients and healthy subjects receiving subcutaneous tesamorelin doses of 1 or 2 mg administered daily during 14 consecutive days were included in the analysis. An open one-compartment model with first- and zero-order absorption and first-order elimination was developed to best describe the data using NONMEM(®) VII. The effect of different covariates on tesamorelin pharmacokinetics was investigated. Model evaluation was performed using predictive checks and non-parametric bootstrap.
  
  
  RESULTS
  Plasma clearance and its interindividual variability [% coefficient of variation (CV)] was estimated to be 1,060 L/h (33.6 %). Volume of distribution was calculated to be 200 L (17.7 %). Age, body size measures, race and health status were not related to tesamorelin pharmacokinetic parameters within the range of covariates studied. The fraction of tesamorelin absorbed by a first-order process is 13.1 % higher on day 14 compared with day 1. Predictive checks and non-parametric bootstrap demonstrated that the model is appropriate in describing the time course of tesamorelin plasma concentrations in both HIV-infected patients and healthy subjects.
  
  
  CONCLUSIONS
  An open one-compartment model with first and zero order absorption processes and linear elimination is suitable to characterize the pharmacokinetics of tesamorelin. The fraction of tesamorelin absorbed by a first-order process evolves with time. No clinically relevant covariates were identified as predictors of tesamorelin pharmacokinetics.
authors.affiliation: Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montreal, QC, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: González-Sales
authors.forename: Olivier
authors.initials: O
authors.lastname: Barrière
authors.forename: Pierre Olivier
authors.initials: PO
authors.lastname: Tremblay
authors.forename: Fahima
authors.initials: F
authors.lastname: Nekka
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mamputu
authors.forename: Sylvie
authors.initials: S
authors.lastname: Boudreault
authors.forename: Mario
authors.initials: M
authors.lastname: Tanguay
mesh_terms: D015992:Body Mass Index; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin