ArticleBritish journal of clinical pharmacology2016
4β-hydroxycholesterol correlates with dose but not steady-state concentration of carbamazepine: indication of intestinal CYP3A in biomarker formation?
Article in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- The CYP3A biomarker 4β-hydroxycholesterol does not improve tacrolimus dose predictions early after kidney transplantation.British journal of clinical pharmacology · 2017Trial
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- Drug Interaction PBPK Modeling: Review of the Literature Exposes the Need for Increased Verification of Model Inputs and Outputs as Part of Credibility Assessment.Clinical and translational science · 2025Review
- Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism.Pharmacological reviews · 2024Review
- Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Interactions Between Direct Oral Anticoagulants (DOACs) and Antiseizure Medications: Potential Implications on DOAC Treatment.CNS drugs · 2023Article
- Impact of type 2 diabetes on in vivo activities and protein expressions of cytochrome P450 in patients with obesity.Clinical and translational science · 2022Article
- Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.European journal of clinical pharmacology · 2022Article
- Short- and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity - a non-randomized three-armed controlled trial.Clinical and translational science · 2022Article
- Effect of Grapefruit Juice Intake on Serum Level of the Endogenous CYP3A4 Metabolite 4β-Hydroxycholesterol-an Interaction Study in Healthy Volunteers.The AAPS journal · 2019Article
- Elevated 4β-hydroxycholesterol/cholesterol ratio in anorexia nervosa patients.Pharmacology research & perspectives · 2018Article
- Gjestad et al. reply to 'Was 4β-hydroxycholesterol ever going to be a useful marker of CYP3A4 activity?' by Neuhoff and Tucker.British journal of clinical pharmacology · 2018Article
- Evaluation of 4β-Hydroxycholesterol and 25-Hydroxycholesterol as Endogenous Biomarkers of CYP3A4: Study with CYP3A-Humanized Mice.The AAPS journal · 2018Article
- 4β-Hydroxycholesterol level significantly correlates with steady-state serum concentration of the CYP3A4 substrate quetiapine in psychiatric patients.British journal of clinical pharmacology · 2017Article
- Impact of genetic and nongenetic factors on interindividual variability in 4β-hydroxycholesterol concentration.European journal of clinical pharmacology · 2017Article
- 4β-Hydroxycholesterol Level in Patients With Rheumatoid Arthritis Before vs. After Initiation of bDMARDs and Correlation With Inflammatory State.Clinical and translational science · 2017Observational
- Recommendations on the Development of a Bioanalytical Assay for 4β-Hydroxycholesterol, an Emerging Endogenous Biomarker of CYP3A Activity.The AAPS journal · 2016Review
- 4β-hydroxycholesterol correlates with dose but not steady-state concentration of carbamazepine: indication of intestinal CYP3A in biomarker formation?British journal of clinical pharmacology · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aim4β-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.
methodsThe 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.
resultsMedian 4βOHC concentration was ~10-fold higher in carbamazepine- vs. levetiracetam-treated patients (650 vs. 54 nmol l(-1) , P < 0.0001). There was a significant, positive correlation between carbamazepine dose and 4βOHC concentration (Spearman r = 0.53, 95% confidence interval [CI] 0.27, 0.72, P < 0.001). No significant correlation between carbamazepine Css and 4βOHC concentration was found (Spearman r = 0.14; 95% CI -0.14, 0.40, P = 0.3). Enzyme-induced females had significantly higher 4βOHC concentrations than males (P < 0.001), while no significant gender difference was found in non-induced patients (P = 0.52).
conclusionSerum concentrations of 4βOHC correlate with presystemic, but not systemic exposure of the CYP3A4 inducer carbamazepine. This suggests a stronger inductive effect of carbamazepine on presystemic than systemic CYP3A4 phenotype and might indicate a role of the intestine in 4βOHC formation. Moreover, CYP3A4 inducibility seems to be higher in females than males.
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