Abstract
Background and Objectives
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.
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Acknowledgments
This work was supported by Mitacs ELEVATE, in partnership with inVentiv Health Canada, NSERC-Industrial Chair in Pharmacometrics and FRQNT. The authors would like to thank the patients, investigators, and their medical, nursing and laboratory staff who participated in the clinical trials included in the present study. Jean-Claude Mamputu is an employee of Theratechnologies Inc., which supported this study. Other authors declare no conflicts of interest.
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González-Sales, M., Barrière, O., Tremblay, P.O. et al. Population Pharmacokinetic Analysis of Tesamorelin in HIV-Infected Patients and Healthy Subjects. Clin Pharmacokinet 54, 285–294 (2015). https://doi.org/10.1007/s40262-014-0202-x
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DOI: https://doi.org/10.1007/s40262-014-0202-x