Paediatric drugs · 2026
Fixed Dosing of Leuprolide Acetate, a GnRH Agonist, in Children with Central Precocious Puberty: A Population Pharmacokinetic Justification.
Клиническое исследование III фазыСтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lim Chay Ngee, Al Yacoub Omar N, Mostafa Nael M, Salem Ahmed Hamed
Аннотация
BACKGROUND: Central precocious puberty is the early onset of puberty due to premature activation of the hypothalamic-pituitary-gonadal axis, which can reduce adult height. Leuprolide, a gonadotropin-releasing hormone agonist, reduces gonadotropin secretion and is the standard treatment for central precocious puberty.
OBJECTIVE: This study aimed to build a population model to describe the pharmacokinetics of a 3-month leuprolide acetate depot formulation in pediatric patients with central precocious puberty, evaluate covariate effects (age and weight) on leuprolide pharmacokinetics, and assess flat-dosing feasibility in pediatrics.
METHODS: Samples from 48 patients (aged 1-10 years) were collected over 24 weeks following the administration of 11.25 and 30 mg of a leuprolide acetate 3-month depot formulation. A population pharmacokinetic model was developed using non-linear mixed-effects modeling (NONMEM). Covariate effects were tested using a forward inclusion and backward elimination approach and exploratory data analysis.
RESULTS: A one-compartment model with immediate and delayed first-order absorption and proportional error model best described leuprolide pharmacokinetics in children. A transit compartment model characterized the delayed absorption. Apparent clearance and volume estimates were 181 L/day and 7.11 L, respectively, which were in alignment with those estimated in adult patients with prostate cancer. The immediate and delayed absorption rate constants were 0.441 day-1 and 0.00879 day-1, respectively. The number of transit compartments and the mean transit time were 3 and 34.1 days, respectively. No covariates significantly affected leuprolide pharmacokinetics.
CONCLUSIONS: The developed model adequately characterized leuprolide pharmacokinetics in pediatrics. No significant covariate effects were observed, supporting the use of a fixed leuprolide dose in pediatrics.
CLINICAL TRIAL REGISTRATION: NCT00635817, registered 13 March, 2008.
OBJECTIVE: This study aimed to build a population model to describe the pharmacokinetics of a 3-month leuprolide acetate depot formulation in pediatric patients with central precocious puberty, evaluate covariate effects (age and weight) on leuprolide pharmacokinetics, and assess flat-dosing feasibility in pediatrics.
METHODS: Samples from 48 patients (aged 1-10 years) were collected over 24 weeks following the administration of 11.25 and 30 mg of a leuprolide acetate 3-month depot formulation. A population pharmacokinetic model was developed using non-linear mixed-effects modeling (NONMEM). Covariate effects were tested using a forward inclusion and backward elimination approach and exploratory data analysis.
RESULTS: A one-compartment model with immediate and delayed first-order absorption and proportional error model best described leuprolide pharmacokinetics in children. A transit compartment model characterized the delayed absorption. Apparent clearance and volume estimates were 181 L/day and 7.11 L, respectively, which were in alignment with those estimated in adult patients with prostate cancer. The immediate and delayed absorption rate constants were 0.441 day-1 and 0.00879 day-1, respectively. The number of transit compartments and the mean transit time were 3 and 34.1 days, respectively. No covariates significantly affected leuprolide pharmacokinetics.
CONCLUSIONS: The developed model adequately characterized leuprolide pharmacokinetics in pediatrics. No significant covariate effects were observed, supporting the use of a fixed leuprolide dose in pediatrics.
CLINICAL TRIAL REGISTRATION: NCT00635817, registered 13 March, 2008.