Trial reportActa pharmacologica Sinica2009
Evaluation of CYP3A activity in humans using three different parameters based on endogenous cortisol metabolism.
Trial report in Acta pharmacologica Sinica, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- The 1β-Hydroxy-Deoxycholic Acid to Deoxycholic Acid Urinary Metabolic Ratio: Toward a Phenotyping of CYP3A Using an Endogenous Marker?Journal of personalized medicine · 2021Article
- Phenotyping of Human CYP450 Enzymes by Endobiotics: Current Knowledge and Methodological Approaches.Clinical pharmacokinetics · 2019Review
- The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction.Pharmacogenomics and personalized medicine · 2018Article
- Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and CYP3A5(*)3 genotype in Chinese renal transplant recipients.Acta pharmacologica Sinica · 2016Article
- Interindividual Variability in Cytochrome P450-Mediated Drug Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2016Review
- Exome-wide association study of bleeding events in patients receiving direct oral anticoagulants.Science progressObservational
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimCurrently, there is considerable debate as to which method is more accurate for measuring the activity of CYP3A in vivo: cortisol 6beta-hydroxylation clearance (Cl(m(6beta))) or the urinary ratio of 6beta-OHF to F (6beta-OHF/F). Furthermore, the value of measuring endogenous levels of cortisol over a 24 h period (AUC(F)) needs to be confirmed. The aim of the present study was to determine which method was most effective at measuring changes in the in vivo activity of CYP3A: AUC(F), Cl(m(6beta)), or 6beta-OHF/F.
methodsA two phase, cross-over design was adopted in this study. A total of 24 subjects (12 males and 12 females) were randomly assigned to one of two groups: the test group subjects were given 250 mg clarithromycin tablets twice a day for a period of 4 d, whereas the control group received a placebo twice daily for a similar period. On d 5 of the study, the last dose of either clarithromycin or placebo was supplemented with an oral dose of 7.5 mg midazolam (MDZ); blood and urine samples were then collected at various times. All samples collected at the same sampling times on d 4 were used to evaluate the effects of MDZ administration on cortisol levels and metabolism. The ratio of 1-hydroxymidazolam (1-OHMDZ) concentration to MDZ concentration at 1 h (MR) was taken as a measure of the in vivo CYP3A activity. AUC(F), Cl(m(6beta)), and 6beta-OHF/F were also used as biomarkers for CYP3A activity.
resultsNo correlations were found (either before or after inhibition) between CYP3A activity and any of the following measures: AUC(F), Cl(m(6beta)), or 6beta-OHF/F (r<0.4, P>0.05). After 4 d of clarithromycin administration, CYP3A activity (MR) decreased by 75% (P=0.000), whereas AUC(F) increased by 19% (P=0.040), and Cl(m(6beta)) and 6beta-OHF/F decreased by 54.2% (P=0.000) and 50% (P=0.003), respectively. No significant changes in AUC(F) (P=0.178), or in the amount of urinary 6beta-OHF (P=0.169), or in F (P=0.391) were found over a 24 h time period, either with or without MDZ administration.
conclusionAlthough Cl(m(6beta)) and 6beta-OHF/F can reflect the decline in CYP3A activity, the impression they provide is neither accurate nor complete. AUC(F) is completely ineffective for evaluating variations in CYP3A activity. MDZ administration had no evident effects on either cortisol metabolism or excretion over a period of 24 h.
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