An In Vitro and In Vivo Evaluation of the Effect of Relacorilant on the Activity of Cytochrome P450 Drug Metabolizing Enzymes
Abstract
Relacorilant is a selective modulator of the glucocorticoid receptor in development for the treatment of several serious diseases. The widely used cocktail method was employed to assess relacorilant's effect on various cytochrome P450 (CYP) drug metabolizing enzymes in vitro and in vivo. Inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2B6, CYP2C8, CYP3A4, and CYP3A5 as well as induction of CYP1A2, CYP2B6, and CYP3A4 were assessed in vitro (relacorilant concentrations up to 10 µM). A clinical study in healthy subjects (n = 27) evaluated the inhibition of CYP3A4, CYP2C8, and CYP2C9 in vivo by administering single doses of probe CYP substrates (midazolam, pioglitazone, and tolbutamide) alone and in combination with relacorilant (350 mg). Pharmacokinetic sampling was conducted, and safety was assessed throughout the study. Pharmacokinetic parameters were evaluated using 90% confidence intervals of the geometric least squares mean ratios of test (probe substrate with relacorilant) vs reference (probe substrate alone) using boundaries of 80% to 125%. In vitro, relacorilant inhibited CYP3A4, CYP2C8, and CYP2C9 but did not meaningfully affect the activity of the other CYP enzymes evaluated. Consistent with the in vitro data, relacorilant was shown to be a strong CYP3A inhibitor in vivo (>8-fold increase in midazolam area under the concentration versus time curve from time zero to the last quantifiable concentration and area under the concentration versus time curve from time zero…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 27 participants or records.
Read the paper
Related studies
- Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence
- Phenolic-protein interactions: insight from in-silico analyses – a review
- In Silico Discovery of Candidate Drugs against Covid-19
- Neuropharmacological Effects of Quercetin: A Literature-Based Review
- In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting
- Effect of Quercetin Rich Onion Extracts on Bacterial Quorum Sensing
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.