Trial reportBritish journal of clinical pharmacology2015
4β-hydroxycholesterol as an endogenous CYP3A marker in cancer patients treated with taxanes.
Trial report in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 18 citations in OpenAlex.
- Influence of probenecid on endoxifen systemic exposure in breast cancer patients on adjuvant tamoxifen treatment.Therapeutic advances in medical oncology · 2022Article
- Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem.Scientific reports · 2021Article
- CYP3A Activity in End-of-Life Cancer Patients Measured by 4β-Hydroxycholesterol/cholesterol Ratio, in Men and Women.Cancers · 2021Article
- Assessment of Hepatic Cytochrome P450 3A Activity Using Metabolic Markers in Patients with Renal Impairment.Journal of Korean medical science · 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
- Distribution of Exogenous and Endogenous CYP3A Markers and Related Factors in Healthy Males and Females.The AAPS journal · 2017Article
- Comparative performance of oral midazolam clearance and plasma 4β-hydroxycholesterol to explain interindividual variability in tacrolimus clearance.British journal of clinical pharmacology · 2016Article
- 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
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTaxanes are anti-cancer agents used to treat several types of solid tumours. They are metabolized by cytochrome P450 (CYP) 3A, displaying a large pharmacokinetic (PK) variability. In this study, we evaluated the endogenous CYP3A4 marker 4β-hydroxycholesterol (4β-OHC) as a potential individual taxane PK predictor.
methodsSerum 4β-OHC and cholesterol concentrations were determined in 291 paclitaxel and 151 docetaxel-treated patients, and were subsequently correlated with taxane clearance.
resultsIn the patients treated with paclitaxel, no clinically relevant correlations between the 4β-OHC or 4β-OHC : cholesterol ratio and paclitaxel clearance were found. In the patients treated with docetaxel, 4β-OHC concentration was weakly correlated with docetaxel clearance in males (r = 0.35 P = 0.01, 95% CI 0.08, 0.58). Of the 10% patients with taxane outlier clearance values, 4β-OHC did correlate with docetaxel clearance in males (r = 0.76, P = 0.03, 95% CI 0.12, 0.95).
conclusionThere was no clinical correlation between paclitaxel clearance and the CYP3A4 activity markers 4β-OHC or the 4β-OHC : cholesterol ratio. A weak correlation was observed between 4β-OHC and docetaxel clearance, but only in males. This endogenous CYP3A4 marker has limited predictive value for taxane clearance in patients.
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