Population pharmacokinetic meta-analysis of vortioxetine in healthy individuals.
Population pharmacokinetic meta-analysis of vortioxetine in healthy individuals.
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DOI：
10.1111/bcpt.12256
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发表时间：
2014-12
影响因子：
3.1
通讯作者：
Naik H
中科院分区：
文献类型：
--
作者：
Areberg J;Petersen KB;Chen G;Naik H
其目的是描述伏替西汀在健康人群中的药代动力学，并评价内在因素和外在因素的影响。26项临床药理学研究的数据被汇集在一起。总共从887名具有相应人口学特征的受试者中收集了21,758个可量化的伏替西汀血药浓度。剂量范围为2.5~75 mg(单剂)和2.5~60 mg(2次/d)。伏替西汀的药代动力学符合二室模型，具有一级吸收、滞后和线性消除，吸收速率常数、口腔清除量和中心分布体积具有个体间误差项。人口平均数为32.7万L/小时和1.97.103万L/小时。平均消除半衰期为65.8小时。研究发现，代谢状态(超代谢、广泛代谢、中等代谢或较差代谢)与年龄对口腔清除量的影响以及身高对中心体积分布的影响被确定为具有统计学意义的协变量参数关系。对于CYP2D6代谢不良者，CL/F约为CYP2D6广泛代谢者的50%。身高对V2/F的影响和年龄对CL/F的影响很小，不被认为与临床相关。最终建立的模型具有较好的可靠性、稳定性和预测性。建立了一个可靠、稳定和可预测的药物动力学模型来描述伏替西汀在健康人群中的药代动力学。
The objective was to describe the pharmacokinetics of vortioxetine and evaluate the effect of intrinsic and extrinsic factors in the healthy population. Data from 26 clinical pharmacology studies were pooled. A total of 21,758 vortioxetine quantifiable plasma concentrations were collected from 887 subjects with corresponding demography. The doses ranged from 2.5 to 75 mg (single dose) and 2.5–60 mg (multiple QD doses). The pharmacokinetics of vortioxetine was best characterised by a two-compartment model with first-order absorption, lag-time and linear elimination, with interindividual error terms for absorption rate constant, oral clearance and central volume of distribution. The population mean was 32.7 L/hr for oral clearance and 1.97·103 L for the central volume of distribution. The average elimination half-life was 65.8 hr. CYP2D6 inferred metabolic status (ultra, extensive, intermediate or poor metabolisers) and age on oral clearance and height on central volume of distribution were identified as statistically significant covariate–parameter relationships. For CYP2D6 poor metabolisers, CL/F was approximately 50% to that seen in CYP2D6 extensive metabolisers. The impact of height on V2/F and age on CL/F was low and not considered to be clinically relevant. The final model was found to be reliable, stable and predictive. A reliable, stable and predictive pharmacokinetic model was developed to characterise pharmacokinetics of vortioxetine in the healthy population.
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影响因子：
3.2
作者：
Chen G;Lee R;Højer AM;Buchbjerg JK;Serenko M;Zhao Z
通讯作者：
Zhao Z
影响因子：
6.7
作者：
Nolin, T. D.;Naud, J.;Pichette, V.
通讯作者：
Pichette, V.
影响因子：
2.9
作者：
Naud, Judith;Nolin, Thomas D.;Pichette, Vincent
通讯作者：
Pichette, Vincent
影响因子：
7.3
作者：
Bang-Andersen, Benny;Ruhland, Thomas;Stensbol, Tine Bryan
通讯作者：
Stensbol, Tine Bryan
影响因子：
9.3
作者：
Steimer, W;Zöpf, K;Leucht, S
通讯作者：
Leucht, S