Optimizing the design of a pharmacokinetic trial to evaluate the dosing scheme of a novel tuberculosis drug in children living with or without HIV.

Autor: Montepiedra G; Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Svensson EM; Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Pharmacy, Uppsala University, Uppsala, Sweden., Wong WK; University of California Los Angeles, Los Angeles, California, USA., Hooker AC; Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2024 Feb; Vol. 13 (2), pp. 270-280. Date of Electronic Publication: 2023 Nov 17.
DOI: 10.1002/psp4.13077
Abstrakt: Pharmacokinetic (PK) studies in children are usually small and have ethical constraints due to the medical complexities of drawing blood in this special population. Often, population PK models for the drug(s) of interest are available in adults, and these models can be extended to incorporate the expected deviations seen in children. As a consequence, there is increasing interest in the use of optimal design methodology to design PK sampling schemes in children that maximize information using a small sample size and limited number of sampling times per dosing period. As a case study, we use the novel tuberculosis drug delamanid, and show how applications of optimal design methodology can result in highly efficient and model-robust designs in children for estimating PK parameters using a limited number of sampling measurements. Using developed population PK models based on available data from adults living with and without HIV, and limited data on children without HIV, competing designs for children living with HIV were derived and assessed based on robustness to model uncertainty.
(© 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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