4β-hydroxycholesterol correlates with dose but not steady-state concentration of carbamazepine: indication of intestinal CYP3A in biomarker formation?

ABSTRACT:

Aim

4β-hydroxycholesterol (4βOHC) is an endogenous CYP3A(4) biomarker, which is elevated by use of the CYP3A4 inducer carbamazepine. Our aim was to compare to what extent serum concentration of 4βOHC correlates with dose (presystemic exposure) and steady-state concentration (systemic exposure) of carbamazepine.

Methods

The study was based on a therapeutic drug monitoring material, including information about daily doses and steady-state concentrations (Css ) of carbamazepine. 4βOHC concentrations were determined in residual serum samples of 55 randomly selected carbamazepine-treated patients and 54 levetiracetam-treated patients (negative controls) by UPLC-APCI-MS/MS after liquid-liquid extraction. Correlation analyses between 4βOHC concentration and daily dose and Css of ca

SUBMITTER: Gjestad C 

PROVIDER: S-EPMC4833147 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature