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哌甲酯在健康成年人中的群体药代动力学，重点关注几种羧酸酯酶1（CES1）变体的新效应和已知效应。

Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants.

作者信息

Lyauk Y K, Stage C, Bergmann T K, Ferrero-Milliani L, Bjerre D, Thomsen R, Dalhoff K P, Rasmussen H B, Jürgens G

机构信息

Roskilde University Hospital, Unit of Clinical Pharmacology, Roskilde, Denmark.

Bispebjerg University Hospital, Department of Clinical Pharmacology, Roskilde, Denmark.

出版信息

Clin Transl Sci. 2016 Dec;9(6):337-345. doi: 10.1111/cts.12423. Epub 2016 Oct 18.

DOI:10.1111/cts.12423
PMID:27754602
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5351003/
Abstract

The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d-MPH plasma exposure.

摘要

本研究的目的是确定显著影响哌甲酯（MPH）药代动力学（PK）的人口统计学和遗传因素，这可能有助于解释个体间差异，并进一步提高MPH的安全性。从122名健康成年人中收集了右旋MPH血浆浓度、人口统计学协变量和羧酸酯酶1（CES1）基因型，并使用非线性混合效应模型进行分析。最能描述数据的结构模型是具有吸收转运室的二室处置模型。最终模型纳入了rs115629050和CES1双倍型的新效应，以及先前报道的rs71647871和体重的效应。对CES1协变量的独立和联合效应评估确定了几个可能导致右旋MPH血浆暴露严重增加的特定风险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fb0/5351003/8e1afa7764ea/CTS-9-337-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fb0/5351003/882905a7cfd7/CTS-9-337-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fb0/5351003/882905a7cfd7/CTS-9-337-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fb0/5351003/5caf5c45b99e/CTS-9-337-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fb0/5351003/cf6f20273514/CTS-9-337-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fb0/5351003/8e1afa7764ea/CTS-9-337-g005.jpg

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