健康成年人血浆和毛发中右旋苯丙胺的群体药代动力学分析。

A Population Pharmacokinetic Analysis of Dextroamphetamine in the Plasma and Hair of Healthy Adults.

作者信息

Roberts Jessica K, Cook Sarah F, Stockmann Chris, Rollins Douglas E, Wilkins Diana G, Sherwin Catherine M T

机构信息

Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.

Center for Human Toxicology, Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.

出版信息

Clin Drug Investig. 2015 Oct;35(10):633-43. doi: 10.1007/s40261-015-0323-5.

DOI:10.1007/s40261-015-0323-5

PMID:26329917

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5572767/

Abstract

BACKGROUND AND OBJECTIVE

Hair is an attractive matrix for amphetamine drug testing; however, little is known about the rate at which amphetamines are deposited into hair. Therefore, the purpose of this study was to determine the pharmacokinetics of oral dextroamphetamine in plasma and quantify the rate of deposition into hair in healthy adults using a linked population pharmacokinetic model.

METHODS

Healthy adults >18 years of age received dextroamphetamine 10 mg orally for 7 days. Plasma samples were collected over 48 h following the final dose, and hair was collected 5 weeks following the first dose. NONMEM 7.2 was used to estimate dextroamphetamine oral absorption rate constant, apparent clearance and volume of distribution of the plasma compartment, the plasma to hair incorporation rate constant, and the apparent volume of distribution in the hair compartment.

RESULTS

Dextroamphetamine pharmacokinetics were well-described by a one-compartment model with combined additive and proportional error for the plasma compartment, which was linked to a single compartment for the hair. Apparent clearance and volume of distribution in the plasma compartment were scaled by current body weight (centered on the mean). Melanin hair concentration was included as a significant covariate on the hair compartment. Absorption rate constant, clearance, and volume of distribution for the plasma compartment were estimated as 0.527 h(-1) (95% CI 0.467-0.586), 28.7 L/h (95% CI 27.1-30.3), and 377 L (95% CI 326-428), respectively. The incorporation rate constant from plasma to hair was 1.60e(-6) h(-1) (95% CI 1.06e(-6)-2.14e(-6)) and apparent volume of distribution in hair was 17.7 mg (95% CI 12.5-22.8).

CONCLUSIONS

A one-compartment plasma model linked to a single compartment for hair successfully described the pharmacokinetics of dextroamphetamine in healthy adults. The volume of distribution and clearance of dextroamphetamine increased with weight, and the volume of distribution of the hair compartment increased with greater melanin concentrations.

摘要

背景与目的

头发是用于苯丙胺类药物检测的一种有吸引力的基质；然而，对于苯丙胺类药物在头发中的沉积速率知之甚少。因此，本研究的目的是使用关联的群体药代动力学模型，确定健康成年人中口服右旋苯丙胺在血浆中的药代动力学，并量化其在头发中的沉积速率。

方法

年龄大于18岁的健康成年人口服10 mg右旋苯丙胺，持续7天。在最后一剂后48小时内采集血浆样本，并在第一剂后5周采集头发样本。使用NONMEM 7.2估计右旋苯丙胺的口服吸收速率常数、表观清除率和血浆室的分布容积、血浆到头发的掺入速率常数以及头发室的表观分布容积。

结果

右旋苯丙胺的药代动力学通过一个一室模型得到很好的描述，该模型对血浆室采用联合加性和比例误差，与头发的单个室相关联。血浆室的表观清除率和分布容积按当前体重（以平均值为中心）进行标度。黑色素头发浓度作为头发室的一个显著协变量被纳入。血浆室的吸收速率常数、清除率和分布容积分别估计为0.527 h⁻¹（95%CI 0.467 - 0.586）、28.7 L/h（95%CI 27.1 - 30.3）和377 L（95%CI 326 - 428）。从血浆到头发的掺入速率常数为1.60e⁻⁶ h⁻¹（95%CI 1.06e⁻⁶ - 2.14e⁻⁶），头发中的表观分布容积为17.7 mg（95%CI 12.5 - 22.8）。