caa a22 4500 60553392X CHVBK 20210128100840.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10928-015-9416-2 doi (NATIONALLICENCE)springer-10.1007/s10928-015-9416-2 Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects [Elektronische Daten] [Mario González-Sales, Olivier Barrière, Pierre Tremblay, Fahima Nekka, Jean-Claude Mamputu, Sylvie Boudreault, Mario Tanguay] 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 2mg 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. Springer Science+Business Media New York, 2015 Phase I nationallicence Clinical trial nationallicence Population pharmacokinetics and pharmacodynamics nationallicence Indirect response nationallicence NONMEM nationallicence González-Sales Mario Université de Montréal, Montreal, Canada aut Barrière Olivier inVentiv Health Clinical, Montreal, Canada aut Tremblay Pierre inVentiv Health Clinical, Montreal, Canada aut Nekka Fahima Université de Montréal, Montreal, Canada aut Mamputu Jean-Claude Theratechnologies Inc, Montreal, Canada aut Boudreault Sylvie inVentiv Health Clinical, Montreal, Canada aut Tanguay Mario inVentiv Health Clinical, Montreal, Canada aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/3(2015-06-01), 287-299 1567-567X 42:3<287 2015 42 10928 https://doi.org/10.1007/s10928-015-9416-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9416-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- González-Sales Mario Université de Montréal, Montreal, Canada aut NATIONALLICENCE 700 1- Barrière Olivier inVentiv Health Clinical, Montreal, Canada aut NATIONALLICENCE 700 1- Tremblay Pierre inVentiv Health Clinical, Montreal, Canada aut NATIONALLICENCE 700 1- Nekka Fahima Université de Montréal, Montreal, Canada aut NATIONALLICENCE 700 1- Mamputu Jean-Claude Theratechnologies Inc, Montreal, Canada aut NATIONALLICENCE 700 1- Boudreault Sylvie inVentiv Health Clinical, Montreal, Canada aut NATIONALLICENCE 700 1- Tanguay Mario inVentiv Health Clinical, Montreal, Canada aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/3(2015-06-01), 287-299 1567-567X 42:3<287 2015 42 10928