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

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.