A comparison of 4-hydroxycholesterol:cholesterol and 6-hydroxycortisol:cortisol as markers of CYP3A4 induction

被引：37
作者：
Arrhen, Yvonne Marde [1 ]
Nylen, Hanna [2 ]
Lovgren-Sandblom, Anita [2 ]
Kanebratt, Kajsa P. [3 ]
Wide, Katarina [4 ]
Diczfalusy, Ulf [2 ]
机构：
[1] Karolinska Univ Hosp, Huddinge, Sweden
[2] Karolinska Inst, Dept Lab Med, Huddinge, Sweden
[3] AstraZeneca R&D, CVGI IMed DMPK, Molndal, Sweden
[4] Karolinska Inst, Dept CLINTEC, Huddinge, Sweden
来源：
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY | 2013年 / 75卷 / 06期
基金：
瑞典研究理事会;
关键词：
CYP3A4; endogenous markers; induction; LC-MS; MS; rifampicin; ENDOGENOUS MARKER; 4-BETA-HYDROXYCHOLESTEROL; HUMANS; 6-BETA-HYDROXYCORTISOL; INHIBITION; RIFAMPICIN;
D O I：
10.1111/bcp.12016
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Aim To compare plasma 4-hydroxycholesterol:cholesterol with urinary 6-hydroxycortisol:cortisol as markers of cytochrome P4503A4 activity before and after treatment with rifampicin for 2 weeks. Method 6-hydroxycortisol and cortisol were determined by liquid chromatography tandem mass spectrometry and 4-hydroxycholesterol was determined by gas chromatographymass spectrometry in three groups of healthy volunteers. Results Induction ratios for 6-hydroxycortisol:cortisol were 1.8, 3.9 and 4.5 for 20mgday1, 100mgday1 or 500mgday1 of rifampicin, respectively. The corresponding ratios for 4-hydroxycholesterol:cholesterol were 1.5, 2.4 and 3.8. Conclusions Plasma 4-hydroxycholesterol:cholesterol gave similar induction ratios to urinary 6-hydroxycortisol:cortisol.
引用
收藏
页码：1536 / 1540
页数：5
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