ArticleBritish journal of clinical pharmacology2008
Time course of the increase in 4beta-hydroxycholesterol concentration during carbamazepine treatment of paediatric patients with epilepsy.
Article in British journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 42 citations in OpenAlex.
- No impact of vitamin D on the CYP3A biomarker 4β-hydroxycholesterol in patients with abnormal glucose regulation.PloS one · 2015Trial
- Endogenous biomarkers for assessing CYP3A4 and CYP2D6 activity: A critical review.Drug metabolism and disposition: the biological fate of chemicals · 2026Review
- Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper.British journal of clinical pharmacology · 2022Review
- 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
- 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
- Evaluation of 4β-Hydroxycholesterol as a Clinical Biomarker of CYP3A4 Drug Interactions Using a Bayesian Mechanism-Based Pharmacometric Model.CPT: pharmacometrics & systems pharmacology · 2014Article
- Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients.The pharmacogenomics journal · 2013Article
- Significant increase in plasma 4β-hydroxycholesterol concentration in patients after kidney transplantation.Journal of lipid research · 2013Article
- Still another activity by the highly promiscuous enzyme CYP3A4: 25-hydroxylation of cholesterol.Journal of lipid research · 2011Article
- Sex and CYP3A5 genotype influence total CYP3A activity: high CYP3A activity and a unique distribution of CYP3A5 variant alleles in Ethiopians.The pharmacogenomics journal · 2011Article
- 4β-Hydroxycholesterol, an endogenous marker of CYP3A4/5 activity in humans.British journal of clinical pharmacology · 2011Review
- 4beta-hydroxycholesterol as an endogenous marker for CYP3A4/5 activity. Stability and half-life of elimination after induction with rifampicin.British journal of clinical pharmacology · 2009Article
- Money makes the world go round: the pervasiveness of pharmacoeconomics.British journal of clinical pharmacology · 2008Article
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4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
what is already known about this subjectCYP3A4 converts cholesterol into 4beta-hydroxycholesterol. We have suggested that 4beta-hydroxycholesterol could be used as a clinical marker for CYP3A4 activity aiding in dose adjustments. The kinetics of 4beta-hydroxycholesterol formation is not known, however, and must be determined in order to establish under what conditions 4beta-hydroxycholesterol can be used as a CYP3A marker. WHAT THIS STUDY ADDS: The concentration of 4beta-hydroxycholesterol increases very slowly during CYP3A4/5 induction in paediatric patients. Whereas induction of CYP3A4/5 was apparently complete within 1-2 weeks of carbamazepine treatment, plasma 4beta-hydroxycholesterol levels continued to increase until at least 8 weeks of treatment. AIMS To investigate the time course of the increase in 4beta-hydroxycholesterol and carbamazepine plasma concentrations during treatment of paediatric patients with epilepsy.
methodsEight paediatric patients with newly diagnosed epilepsy were studied. Blood samples were drawn before and after about 1, 2, 4, 8 and 16 weeks of carbamazepine treatment. The plasma concentrations of 4beta-hydroxycholesterol were determined by gas chromatography-mass spectrometry and carbamazepine and its epoxide metabolite by high-performance liquid chromatography.
resultsThe basal plasma concentrations of 4beta-hydroxycholesterol showed a large range of observed values between 18 and 99 ng ml(-1). Carbamazepine treatment increased mean plasma 4beta-hydroxycholesterol significantly already after 1 week of treatment (from 43 to 80 ng ml(-1), P < 0.001). 4beta-Hydroxycholesterol concentrations continued to increase until at least 8 weeks of treatment and the concentrations in the final samples (8-23 weeks of treatment) varied between 122 and 494 ng ml(-1). Plasma concentrations of carbamazepine and its epoxide metabolite reached steady state at 1-2 weeks after last dose change.
conclusionsCarbamazepine treatment of paediatric patients with epilepsy resulted in an induction of CYP3A4/5 and a concomitant increase in plasma 4beta-hydroxycholesterol. Whereas the induction of CYP3A4/5 was apparently complete after 1-2 weeks, the increase in 4beta-hydroxycholesterol continued for several weeks. Thus CYP3A4 activity is not the only determinant of the circulating level of 4beta-hydroxycholesterol. Additional factors such as transport and storage or presence of another enzyme may thus be of importance.
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