Pilot Study to Assess the Contribution of UGT2B17 and Associated Genetic Polymorphisms on the Pharmacokinetics of Diclofenac Alone and Upon Co-administration With Curcumin
Washington State University
Summary
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.
Description
Diclofenac, a widely used non-steroidal anti-inflammatory drug, has been linked to severe adverse effects such as gastrointestinal ulcers and bleeding and cardiotoxicity. Based on cardiotoxicity reports, US and European regulatory agencies withdrew over-the-counter (OTC) diclofenac, requiring the drug to be a prescription-only medication. However, diclofenac remains OTC in many countries, including Australia, China, and India, among others. Reported metabolic pathways of diclofenac in the liver are mediated by the prominent drug metabolizing enzyme, cytochrome P450 (CYP) 2C9, and the conjugati…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- Yes
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 metho…
Interventions
- DrugDiclofenac
25 mg capsule
- Dietary Supplementcurcumin
2,000 mg tablet
Location
- Washington State University College of Pharmacy and Pharmaceutical SciencesSpokane, Washington