title: Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects.
abstract: The objective of this analysis was to characterize the time course of selected pharmacodynamic (PD) markers of tesamorelin: growth hormone (GH) and insulin-like growth factor (IGF-1) concentrations in HIV-infected patients and healthy volunteers. A total of 41 subjects in Phase I trials receiving subcutaneous daily doses of 1 or 2 mg of tesamorelin during 14 consecutive days were included in this analysis. A previous pharmacokinetic (PK) model of tesamorelin was used as the input function for the PD model of GH. Tesamorelin was hypothesized to stimulate the secretion of GH in an "episodic" manner, i.e., for a finite duration of time. The resulting PK/PD model of GH was used to describe the time course of IGF-1. The effect of age, body weight, body mass index, sex, race, and health status on the model parameters was evaluated. The model was qualified using predictive checks and non-parametric bootstrap. Within the range of the values evaluated no covariates were significantly associated with GH or IGF-1 model parameters. Model evaluation procedures indicated accurate prediction of the selected pharmacodynamic markers. The time course of GH and IGF-1 concentrations following multiple doses of tesamorelin were well predicted by the sequential PK/PD model developed using Phase I data.
authors.affiliation: Université de Montréal, Montreal, 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: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D064368:Healthy Volunteers; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; C479538:tesamorelin