为何干血斑是CYP1A2表型分析的理想工具。

Why dried blood spots are an ideal tool for CYP1A2 phenotyping.

作者信息

De Kesel Pieter M M, Lambert Willy E, Stove Christophe P

机构信息

Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium.

出版信息

Clin Pharmacokinet. 2014 Aug;53(8):763-71. doi: 10.1007/s40262-014-0150-5.

DOI:10.1007/s40262-014-0150-5

PMID:24980692

Abstract

BACKGROUND AND OBJECTIVE

Dried blood spot (DBS) sampling has gained wide interest in bioanalysis during the last decade and has already been successfully applied in pharmacokinetic and phenotyping studies. However, all of the available phenotyping studies used small datasets and did not include a systematic evaluation of DBS-specific parameters. The latter is important since several of these factors still challenge the breakthrough of DBS in routine practice. In this study, caffeine and paraxanthine are determined in capillary DBS, venous DBS, whole blood and plasma for cytochrome P450 (CYP) 1A2 phenotyping. The aim of this study was to explore the usefulness of DBS as a tool for CYP1A2 phenotyping.

METHODS

A CYP1A2 phenotyping study was conducted in 73 healthy volunteers who received a 150 mg oral dose of caffeine. Six hours post-administration, caffeine and paraxanthine concentrations and paraxanthine:caffeine molar concentration ratios, i.e., the actual CYP1A2 phenotyping indices, were determined in capillary DBS (obtained by non-volumetric application, direct from the fingertip), venous DBS, whole blood, and plasma. Furthermore, the impact of DBS-specific parameters, including hematocrit, volume spotted, and punch location, was evaluated.

RESULTS

Concentrations of caffeine and paraxanthine in capillary DBS were, respectively, on average 12.7 and 13.8% lower than those in venous DBS and 31.5 and 33.1% lower than those in plasma. While these differences were statistically significant (p < 0.001), no significant difference was observed between the paraxanthine:caffeine molar ratios in the distinct evaluated matrices (p ≥ 0.053). This ratio also alleviated the impact of hematocrit and volume spotted.

CONCLUSIONS

Using the largest DBS-based phenotyping study to date, we have demonstrated that CYP1A2 phenotyping in capillary DBS is a valid and convenient alternative for the classical plasma-based approach. Additionally, we have provided an objective basis as to why DBS are an ideal tool for CYP1A2 phenotyping.

摘要

背景与目的

在过去十年中，干血斑（DBS）采样在生物分析领域引起了广泛关注，并已成功应用于药代动力学和表型研究。然而，所有现有的表型研究都使用了小数据集，且未对DBS特异性参数进行系统评估。后者很重要，因为其中一些因素仍然阻碍着DBS在常规实践中的突破。在本研究中，测定了用于细胞色素P450（CYP）1A2表型分析的毛细血管DBS、静脉DBS、全血和血浆中的咖啡因和副黄嘌呤。本研究的目的是探索DBS作为CYP1A2表型分析工具的实用性。

方法

对73名健康志愿者进行了一项CYP1A2表型研究，这些志愿者口服了150mg咖啡因。给药后6小时，测定了毛细血管DBS（通过非定量应用直接从指尖获得）、静脉DBS、全血和血浆中的咖啡因和副黄嘌呤浓度以及副黄嘌呤：咖啡因摩尔浓度比，即实际的CYP1A2表型分析指标。此外，评估了DBS特异性参数的影响，包括血细胞比容、点样体积和打孔位置。