Mario González-Sales (1,2), Olivier Barrière (2), Pierre Olivier Tremblay (2), Fahima Nekka (1), Jean-Claude Mamputu (3), Sylvie Boudreault (2), Mario Tanguay (1,2).
1) Université de Montréal, Montréal, Canada, (2) Inventiv Health Clinical, Montréal, Canada, (3) Theratechnologies Inc, Montréal, Canada.
Objectives: Tesamorelin is a synthetic analogue of growth hormone-releasing factor, which significantly decrease visceral adipose tissue and improve metabolic and patient-reported outcome parameters in HIV-infected patients with excess abdominal fat.[1] The aim of this study was to characterize the population pharmacokinetics of tesamorelin in HIV-infected patients and healthy subjects from data of two phase I clinical trials.
Methods: A total of 38 patients 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 between subject variability (%) was estimated to be 1060 L/h (33.8). Volume of distribution was calculated to be 201 L (17.9). Age, body size measures and race were not related to tesamorelin pharmacokinetic parameters within the range of covariates studied. The fraction of tesamorelin absorbed by a first order process is 15.6% higher on day 14 compared to 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.
References:
[1] Stanley TL, Falutz J, Marsolais C, et al. Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin. Clin Infect Dis (2012) 54(11): 1642-51.
Reference: PAGE 23 () Abstr 3132 [www.page-meeting.org/?abstract=3132]
Poster: Drug/Disease modeling - Other topics