Background:

4β-hydroxy Cholesterol is an endogenous marker for CYP3A4/5 activity [1].

Cytochome P450 3A4 (CYP3A4) and CYP3A5 are important drug-metabolizing enzymes that oxidize small foreign organic molecules, such as toxins or drugs, and remove them from the body. They exhibit a large variation in hepatic expression and biological activity between different individuals. Patients treated with drugs known to be strong inducers of CYP3A4/5 have highly elevated levels of 4β-hydroxycholesterol in the circulation [1].

4β-hydroxy Cholesterol, an endogenous oxysterol found in human circulation, is formed from cholesterol by cytochrome P450 (CYP) 3A4 and CYP3A5. In 12 different occasions during a 3-month period, The CVs for 4β-hydroxycholesterol ranged from 4.8 to 13.2% with an average CV of 7.1% at an average concentration of 30.8 ng/ml. In 24 volunteers treated with rifampicin, a strong CYP3A4/5 inducer, 4β-hydroxycholesterol increased in a dose-dependent way, while the isomer 4α-hydroycholesterol was not influenced by rifampicin treatment. These results suggested that 4β-hydroxy Cholesterol is an endogenous marker for CYP3A4/5 activity [1].

Reference:
[1].  Diczfalusy U, Kanebratt KP, Bredberg E, et al. 4beta-hydroxycholesterol as an endogenous marker for CYP3A4/5 activity. Stability and half-life of elimination after induction with rifampicin. Br J Clin Pharmacol. 2009 Jan;67(1):38-43.