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

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 carbamazepine, respectively, were performed by Spearman's tests. In addition, 4βOHC concentrations in females vs. males were compared in induced and non‐induced patients. Results Median 4βOHC concentration was ~10‐fold higher in carbamazepine‐ vs. levetiracetam‐treated patients (650 vs. 54 nmol l−1, P