ArticleFrontiers in genetics2020
Inherited and Acquired Determinants of Hepatic CYP3A Activity in Humans.
Article in Frontiers in genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- Impact ofTherapeutic advances in psychopharmacology · 2025Article
- Pharmacokinetics, Pharmacodynamics, and Side Effects of Midazolam: A Review and Case Example.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The effect of genetic variants in the transcription factor TSPYL family on the CYP3A4 mediated cyclosporine metabolism in kidney transplant patients.Clinical and translational science · 2024Article
- Development of radioiodine-labeled mequitazine for evaluation of hepatic CYP2D activity.Frontiers in pharmacology · 2024Article
- Understanding and addressing the needs of people with cystic fibrosis in the era of CFTR modulator therapy.The Lancet. Respiratory medicine · 2023Review
- Intraindividual Variability in Absolute Bioavailability and Clearance of Midazolam in Healthy Individuals.Clinical pharmacokinetics · 2023Article
- Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio.International journal of molecular sciences · 2022Article
- Transcription Factors and ncRNAs Associated withBiomedicines · 2022Article
- Regulatory variants in a novel distal enhancer regulate the expression of CYP3A4 and CYP3A5.Clinical and translational science · 2022Article
- Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human CYP3A enzymes (including CYP3A4 and CYP4A5) metabolize about 40% of all drugs and numerous other environmental and endogenous substances. CYP3A activity is highly variable within and between humans. As a consequence, therapy with standard doses often results in too low or too high blood and tissue concentrations resulting in therapeutic failure or dose-related adverse reactions. It is an unanswered question how much of the big interindividual variation in CYP3A activity is caused by genetic or by environmental factors. This question can be answered by the twin study approach. Using midazolam as CYP3A probe drug, we studied 43 monozygotic and 14 dizygotic twins and measured midazolam and its metabolite 1-OH-midazolam. In addition, endogenous biomarkers of CYP3A activity, 4ß-OH-cholesterol and 6ß-OH-cortisol, were analyzed. Additive genetic effects accounted for only 15% of the variation in midazolam AUC, whereas 48% was attributed to common environmental factors. In contrast, 73, 56, and 31% of 1-OH-midazolam, 4ß-OH-cholesterol and 6ß-OH-cortisol variation was due to genetic effects. There was a low phenotypic correlation between the four CYP3A biomarkers. Only between midazolam and its 1-OH-metabolite, and between midazolam and 6ß-OH-cortisol we found significant bivariate genetic correlations. Midazolam AUC differed depending on the
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