Trial reportClinical pharmacology and therapeutics2012
UGT2B17 genetic polymorphisms dramatically affect the pharmacokinetics of MK-7246 in healthy subjects in a first-in-human study.
Trial report in Clinical pharmacology and therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06053411 (Pilot Study to Assess the Contribution of UGT2B17 and Associated Genetic Polymorphisms on the Pharmacokinetics of Diclofenac Alone and Upon Co-administration With Curcumin), which is not on this map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Pilot Study to Assess the Contribution of UGT2B17 and Associated Genetic Polymorphisms on the Pharmacokinetics of Diclofenac Alone and Upon Co-administration With Curcumin
Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers.Clinical pharmacology in drug development · 2016Trial
- The liver proteome of individuals with a natural UGT2B17 complete deficiency.Scientific reports · 2025Article
- Differential Tissue Abundance of Membrane-Bound Drug Metabolizing Enzymes and Transporter Proteins by Global Proteomics.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Article
- Comparison of Relative Activity versus Relative Expression Factors (RAF versus REF) in Predicting Glucuronidation Mediated Drug Clearance Using Recombinant UGTs.Pharmaceutical research · 2024Article
- Intestinal Metabolism of Diclofenac by Polymorphic UGT2B17 Correlates with its Highly Variable Pharmacokinetics and Safety across Populations.Clinical pharmacology and therapeutics · 2023Article
- Dimethandrolone, a Potential Male Contraceptive Pill, is Primarily Metabolized by the Highly Polymorphic UDP-Glucuronosyltransferase 2B17 Enzyme in Human Intestine and Liver.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- PET Imaging of GPR44 by Antagonist [Biomedicines · 2021Article
- Variability in Human In Vitro Enzyme Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Normalized Testosterone Glucuronide as a Potential Urinary Biomarker for Highly Variable UGT2B17 in Children 7-18 Years.Clinical pharmacology and therapeutics · 2020Article
- Factors Affecting Interindividual Variability of Hepatic UGT2B17 Protein Expression Examined Using a Novel Specific Monoclonal Antibody.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Quantitative characterization of UDP-glucuronosyltransferase 2B17 in human liver and intestine and its role in testosterone first-pass metabolism.Biochemical pharmacology · 2018Article
- Effect of Dose and 5α-Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone.Clinical and translational science · 2018Article
- Hepatic Abundance and Activity of Androgen- and Drug-Metabolizing Enzyme UGT2B17 Are Associated with Genotype, Age, and Sex.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Article
- Regulation of Hepatic UGT2B15 by Methylation in Adults of Asian Descent.Pharmaceutics · 2018Article
- Progress in Prediction and Interpretation of Clinically Relevant Metabolic Drug-Drug Interactions: a Minireview Illustrating Recent Developments and Current Opportunities.Current pharmacology reports · 2017Review
- Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver.Human molecular genetics · 2014Article
- Drug-drug interaction studies: regulatory guidance and an industry perspective.The AAPS journal · 2013Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MK-7246, an antagonist of the chemoattractant receptor on T helper type 2 (Th2) cells, is being developed for the treatment of respiratory diseases. In a first-in-human study, we investigated whether genetic polymorphisms contributed to the marked intersubject variability in the pharmacokinetics of MK-7246 and its glucuronide metabolite M3. Results from in vitro enzyme kinetic studies suggested that UGT2B17 is probably the major enzyme responsible for MK-7246 metabolism in both the liver and the intestine. As compared with those with the UGT2B17*1/*1 wild-type genotype, UGT2B17*2/*2 carriers, who possess no UGT2B17 protein, had 25- and 82-fold greater mean dose-normalized values of area under the plasma concentration-time curve (AUC) and peak concentration of MK-7246, respectively, and a 24-fold lower M3-to-MK-7246 AUC ratio. The apparent half-life of MK-7246 was not as variable between these two genotypes. Therefore, the highly variable pharmacokinetics of MK-7246 is attributable primarily to the impact of UGT2B17 genetic polymorphisms and extensive first-pass metabolism of MK-7246.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.