Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents.
Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents.
复制标题
DOI：
10.1111/cts.12803
复制
发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee
中科院分区：
文献类型：
--
作者：
Ge S;Mendley SR;Gerhart JG;Melloni C;Hornik CP;Sullivan JE;Atz A;Delmore P;Tremoulet A;Harper B;Payne E;Lin S;Erinjeri J;Cohen-Wolkowiez M;Gonzalez D;Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee
胃复安通常用于胃食管反流。本研究的目的是建立一个儿童群体药代动力学（PopPK）模型，用于模拟临床实践中使用的甲氧氯普胺给药后的暴露量。从按照标准治疗接受肠内或肠外甲氧氯普胺治疗的儿科患者中收集药代动力学数据，并使用NONMEM同时拟合这些数据。在模型中先验地包括体重的异速生长比例。使用最终模型，模拟虚拟患者每6小时口服0.1或0.15 mg/kg后的稳态最大浓度（Css，max）和0 - 6小时稳态时甲氧氯普胺血药浓度-时间曲线下面积（AUCss，0- 6 h），并与先前报告的婴儿胃食管反流毒性或疗效相关范围进行比较。具有一级吸收的二室模型最佳表征了50例患者的87个浓度测量值（中位[范围]出生后年龄为8.89岁[0.01-19.13]）。有20名婴儿（≤ 2岁）、9名儿童（2岁至≤ 12岁）和21名青少年（> 12岁）。体重是最终模型中纳入的唯一协变量。对于> 75%的虚拟患者，模拟的Css，max和AUCss，0- 6 h估计值在婴儿胃食管反流有效性相关范围内;然而，在< 2岁的虚拟患者中预测的暴露量略低。我们的研究表明，甲氧氯普胺肠内剂量为0.1 mg/kg，每6小时一次，这是以前推荐的儿科患者，结果模拟暴露通常在建议的范围内治疗胃食管反流。
Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical practice. Opportunistic pharmacokinetic data were collected from pediatric patients receiving enteral or parenteral metoclopramide per standard of care and these data were simultaneously fitted using NONMEM. Allometric scaling with body weight was included a priori in the model. Using the final model, the steady‐state maximum concentrations (Css,max) and the area under the metoclopramide plasma concentration‐time curve at steady state from 0 to 6 hours (AUCss,0–6h) were simulated following 0.1 or 0.15 mg/kg orally every 6 hours in virtual patients, and compared with previously reported ranges associated with toxicity or the efficacy for gastroesophageal reflux in infants. A two‐compartment model with first‐order absorption best characterized 87 concentration measurements from 50 patients (median [range] postnatal age of 8.89 years [0.01–19.13]). There were 20 infants (≤ 2 years), 9 children (2 years to age ≤ 12 years), and 21 adolescents (> 12 years). Body weight was the only covariate included in the final model. For > 75% of virtual patients, simulated Css,max and AUCss,0–6h estimates were within the range associated with efficacy for gastroesophageal reflux in infants; however, slightly lower exposures were predicted in virtual patients < 2 years. Our study suggests that a metoclopramide enteral dose of 0.1 mg/kg every 6 hours, which was previously recommended for pediatric patients, results in simulated exposure generally within suggested ranges for the treatment of gastroesophageal reflux.
登录
查看更多内容
影响因子：
5.1
作者：
SCHWARTZ, GJ;GAUTHIER, B
通讯作者：
GAUTHIER, B
DOI：
10.1097/00005176-198607000-00008
发表时间：
1986-07-01
影响因子：
2.9
作者：
FORBES, D;HODGSON, M;HILL, R
通讯作者：
HILL, R
影响因子：
4.5
作者：
GREVEL, J;WHITING, B;BATEMAN, DN
通讯作者：
BATEMAN, DN
影响因子：
8.8
作者：
LIN, DM;FURST, SR;RODARTE, A
通讯作者：
RODARTE, A
影响因子：
6.1
作者：
Lindbom, L;Ribbing, J;Jonsson, EN
通讯作者：
Jonsson, EN