Interaction Clinical Trial
Official title:
Pilot Study to Assess the Contribution of UGT2B17 and Associated Genetic Polymorphisms on the Pharmacokinetics of Diclofenac Alone and Upon Co-administration With Curcumin
The purpose of this pilot study is to gather preliminary data on the (1) contribution of the understudied drug metabolizing enzyme, UDP-glucuronosyltransferase (UGT) 2B17, to the metabolism of a widely used medication, diclofenac, and (2) impact of the UGT2B17 inhibitor and natural product, curcumin, on diclofenac pharmacokinetics. Results will inform future studies aimed to assess the effects of UGT2B17 genetic polymorphisms and co-consumed xenobiotics on the pharmacokinetics and toxicity risk of diclofenac and other UGT2B17 drug substrates.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | August 18, 2024 |
Est. primary completion date | August 18, 2024 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: - Aged from 18-64 years and healthy - Not taking any medications (prescription and non-prescription) or dietary/herbal supplements known to alter the pharmacokinetics of diclofenac or curcumin - Willing to abstain from consuming caffeinated beverages or other caffeine-containing products the evening before and morning of the first day of each study arm - Willing to abstain from consuming any alcoholic beverages for one day prior to any study day, during the 14-hour inpatient days, and for the outpatient visit(s) following the 14-hour days - Willing to use a secondary method of birth control that does not include the introduction or discontinuance of hormonal-based birth control (such as abstinence, copper IUD, or condoms) - Have the time to participate - Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for the subject to comply with the requirements of the study Exclusion Criteria: - Under the age of 18 or over the age of 65 years - Smoke/vape/chew tobacco products - Use cannabis products, including marijuana, hemp, and other THC- or CBD-containing products - Have any current major illness or chronic illness such as (but not limited to) kidney disease, hepatic disease, diabetes mellitus, hypertension, coronary artery disease, chronic obstructive pulmonary disease, cancer, or HIV/AIDS - History of anemia or any other significant hematologic disorder - History of drug or alcohol addiction or major psychiatric illness - Pregnant or nursing or plan to become pregnant within 3 weeks after participation - History of allergy intolerance to diclofenac or curcumin - Taking concomitant medications, both prescription and non-prescription (including dietary supplements/herbal products), known to alter the pharmacokinetics of diclofenac or curcumin - Taking any turmeric spice or curcumin supplement - Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise participant safety or quality of the data - Out-of-range clinical laboratory value that the study physician considers participation in the study a health risk |
Country | Name | City | State |
---|---|---|---|
United States | Washington State University College of Pharmacy and Pharmaceutical Sciences | Spokane | Washington |
Lead Sponsor | Collaborator |
---|---|
Washington State University |
United States,
Ahire D, Heyward S, Prasad B. Intestinal Metabolism of Diclofenac by Polymorphic UGT2B17 Correlates with its Highly Variable Pharmacokinetics and Safety across Populations. Clin Pharmacol Ther. 2023 Jul;114(1):161-172. doi: 10.1002/cpt.2907. Epub 2023 Apr 29. — View Citation
Schjerning AM, McGettigan P, Gislason G. Cardiovascular effects and safety of (non-aspirin) NSAIDs. Nat Rev Cardiol. 2020 Sep;17(9):574-584. doi: 10.1038/s41569-020-0366-z. Epub 2020 Apr 22. — View Citation
Wang YH, Trucksis M, McElwee JJ, Wong PH, Maciolek C, Thompson CD, Prueksaritanont T, Garrett GC, Declercq R, Vets E, Willson KJ, Smith RC, Klappenbach JA, Opiteck GJ, Tsou JA, Gibson C, Laethem T, Panorchan P, Iwamoto M, Shaw PM, Wagner JA, Harrelson JC. UGT2B17 genetic polymorphisms dramatically affect the pharmacokinetics of MK-7246 in healthy subjects in a first-in-human study. Clin Pharmacol Ther. 2012 Jul;92(1):96-102. doi: 10.1038/clpt.2012.20. Epub 2012 Jun 6. — View Citation
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Xue Y, Sun D, Daly A, Yang F, Zhou X, Zhao M, Huang N, Zerjal T, Lee C, Carter NP, Hurles ME, Tyler-Smith C. Adaptive evolution of UGT2B17 copy-number variation. Am J Hum Genet. 2008 Sep;83(3):337-46. doi: 10.1016/j.ajhg.2008.08.004. Epub 2008 Aug 28. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Diclofenac area under the concentration vs. time curve (AUC) in UGT2B17 extensive metabolizers (EMs) | Diclofenac AUC in UGT2B17 EMs | 0-12 hours | |
Primary | Diclofenac AUC in poor metabolizers (PMs) | Diclofenac AUC in UGT2B17 PMs | 0-12 hours | |
Primary | Diclofenac AUC in EMs in the presence of curcumin | Diclofenac AUC in UGT2B17 EMs in the presence of curcumin | 0-12 hours | |
Primary | Diclofenac maximum concentration (Cmax) in EMs | Diclofenac Cmax in UGT2B17 EMs | 0-12 hours | |
Primary | Diclofenac Cmax in PMs | Diclofenac Cmax in UGT2B17 PMs | 0-12 hours | |
Primary | Diclofenac Cmax in EMs in the presence of curcumin | Diclofenac Cmax in UGT2B17 EMs in the presence of curcumin | 0-12 hours | |
Primary | Diclofenac renal clearance (CLr) in EMs | Diclofenac CLr in UGT2B17 EMs | 0-12 hours | |
Primary | Diclofenac CLr in PMs | Diclofenac CLr in UGT2B17 PMs | 0-12 hours | |
Primary | Diclofenac CLr in EMs in the presence of curcumin | Diclofenac CLr in UGT2B17 EMs in the presence of curcumin | 0-12 hours | |
Primary | Diclofenac half-life (t1/2) in EMs | Diclofenac t1/2 in UGT2B17 EMs | 0-12 hours | |
Primary | Diclofenac half-life (t1/2) in PMs | Diclofenac t1/2 in UGT2B17 PMs | 0-12 hours | |
Primary | Diclofenac half-life (t1/2) in EMs in the presence of curcumin | Diclofenac t1/2 in UGT2B17 EMs in the presence of curcumin | 0-12 hours |
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