Yujin Lee, Woori Chae, Seonghae Yoon, Jae-Yong Chung, Joo-Youn Cho
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引用次数: 4
Abstract
Cytochrome P450 (CYP) 3A enzymes, the most important phase 1 drug-metabolizing enzymes, are responsible for 50% of the metabolism of clinically used drugs. CYP3A activity varies widely among individuals, which can affect the probability of adverse drug reactions and drug-drug interactions mediated by the induction or inhibition of the enzyme. Hence, it is important to be able to predict CYP3A activity in individuals to reduce the incidence of unexpected drug responses. To specifically and quickly measure CYP3A activity, we developed method based on gas chromatography interfaced with triple-quadrupole mass spectrometry for the quantification of cortisol, cortisone, 6β-hydroxycortisol, and 6β-hydroxycortisone simultaneously in urine and 4β-hydroxycholesterol in plasma. The results were calculated based on charcoal-stripped steroid-free urine and plasma control samples. The accuracy and precision were 93.18% to 110.0% and 1.96% to 5.34%, respectively. This method was then applied to measure endogenous steroids from urine and plasma samples of healthy Korean males and females. The calibration curves of all analytes showed good linearity with a correlation coefficient (r2) that ranged from 0.9953 to 0.9999. Therefore, this validated method can be used to measure endogenous biomarkers to predict CYP3A activity and might be applicable in the prediction of CYP3A-mediated drug interactions of new drug candidates.
期刊介绍:
Translational and Clinical Pharmacology (Transl Clin Pharmacol, TCP) is the official journal of the Korean Society for Clinical Pharmacology and Therapeutics (KSCPT). TCP is an interdisciplinary journal devoted to the dissemination of knowledge relating to all aspects of translational and clinical pharmacology. The categories for publication include pharmacokinetics (PK) and drug disposition, drug metabolism, pharmacodynamics (PD), clinical trials and design issues, pharmacogenomics and pharmacogenetics, pharmacometrics, pharmacoepidemiology, pharmacovigilence, and human pharmacology. Studies involving animal models, pharmacological characterization, and clinical trials are appropriate for consideration.