Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects
| Autor: | Sylvie Boudreault, Jean-Claude Mamputu, Olivier Barrière, Mario Tanguay, Pierre Olivier Tremblay, Mario González-Sales, Fahima Nekka |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Coefficient of variation Population HIV Infections Growth Hormone-Releasing Hormone law.invention Body Mass Index Pharmacokinetics Randomized controlled trial law Internal medicine medicine Humans Pharmacology (medical) education Pharmacology Volume of distribution education.field_of_study business.industry Healthy subjects Middle Aged Tesamorelin Endocrinology Female business Body mass index medicine.drug |
| Zdroj: | Clinical pharmacokinetics. 54(3) |
| ISSN: | 1179-1926 |
| Popis: | 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. 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. 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. 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. |
| Databáze: | OpenAIRE |
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