PDF(Pubmed)
Abstract：
Phenytoin is a first-line antiepileptic drug with narrow therapeutic range and follows non-linear pharmacokinetics. Pharmacokinetics of phenytoin have been studied in plasma matrix before, however, there were several disadvantages. This study aimed to obtain partial validation data of the analytical method and the pharmacokinetic profile of phenytoin in Dried Blood Spot (DBS) of six healthy subjects. DBS has the advantage of only requiring small sample volumes and could be transported more efficiently. Phenytoin along with carbamazepine as the chosen internal standard was analyzed with a reversed-phase high performance-liquid chromatography system and a photodiode array detector at 205 nm. The results of partial validation, which evaluated the linearity, within-run accuracy, and precision, were within the criteria acceptance range. The pharmacokinetic profile showed that average AUC0-t was 83.81 ± 37.32 μg.h/mL and AUC0-∞ was 83.65 ± 38.89 μg.h/mL with an average ratio of 93%. Previous study quantifying phenytoin in the plasma matrix found the average AUC0-t was 39.41 ± 8.57 µg.h/mL and AUC0-∞ was 42.94 ± 9.55 µg.h/mL. Despite the difference between parameters of phenytoin analyzed in DBS and plasma matrices, the pharmacokinetic profiles obtained from both matrices were similar indicated by comparable concentration-time curves, thus, proving that DBS matrix can be used interchangeably with the plasma matrix as a more comfortable and effective alternative to phenytoin quantification in blood.
摘要：
苯妥英是一线抗癫痫药物，治疗范围窄，具有非线性药代动力学。之前已经在血浆基质中研究了苯妥英的药代动力学，然而,有几个缺点。本研究旨在获得六位健康受试者干血斑（DBS）中苯妥英的分析方法和药代动力学特征的部分验证数据。DBS具有仅需要小样品体积的优点,并且可以更有效地运输。用反相高效液相色谱系统和205nm的光电二极管阵列检测器分析了苯妥英和卡马西平作为内标。部分验证的结果，它评估了线性度，运行内精度，和精度，在标准接受范围内。药代动力学曲线显示平均AUC0-t为83.81±37.32μg。h/mL和AUC0-∞为83.65±38.89μg。h/mL,平均比例为93%。先前定量血浆基质中苯妥英的研究发现，平均AUC0-t为39.41±8.57µg。h/mL和AUC0-∞为42.94±9.55µg。h/mL。尽管在DBS和血浆基质中分析的苯妥英参数之间存在差异，从两种基质中获得的药代动力学曲线相似，通过可比的浓度-时间曲线表明，因此，证明DBS基质可以与血浆基质互换使用，作为血液中苯妥英定量的更舒适和有效的替代方法。
