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Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects

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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.

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Acknowledgments

This work was supported by Mitacs ELEVATE, in partnership with inVentiv Health, NSERC-Industrial Chair in Pharmacometrics and FRQNT. The authors would like to thank the reviewers of this manuscript for their careful reading and suggestions.

Conflict of interest

Jean-Claude Mamputu is an employee of Theratechnologies Inc., which supported this study. Other authors declare no conflict of interest.

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Authors and Affiliations

  1. Université de Montréal, Montreal, Canada

    Mario González-Sales & Fahima Nekka

  2. inVentiv Health Clinical, Montreal, Canada

    Mario González-Sales, Olivier Barrière, Pierre Olivier Tremblay, Sylvie Boudreault & Mario Tanguay

  3. Theratechnologies Inc, Montreal, Canada

    Jean-Claude Mamputu

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  1. Mario González-Sales
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  2. Olivier Barrière
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  3. Pierre Olivier Tremblay
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  4. Fahima Nekka
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  5. Jean-Claude Mamputu
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  6. Sylvie Boudreault
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  7. Mario Tanguay
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Correspondence to Fahima Nekka.

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González-Sales, M., Barrière, O., Tremblay, P.O. et al. Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects. J Pharmacokinet Pharmacodyn 42, 287–299 (2015). https://doi.org/10.1007/s10928-015-9416-2

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  • DOI: https://doi.org/10.1007/s10928-015-9416-2

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