title: Effect of Resveratrol Treatment on the Pharmacokinetics of Diclofenac in Healthy Human Volunteers.
abstract: The purpose of the present study was to assess the effect of resveratrol (RSV) treatment on the pharmacokinetics of diclofenac (DIC) in healthy human volunteers. The open-label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered daily for 10 days during treatment phase. A single dose of DIC 100 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after DIC dosing and analyzed by HPLC. Treatment with RSV significantly enhanced maximum plasma concentration (Cmax) (1.73 to 2.91 µg/mL), area under the curve (AUC) (5.05 to 9.95 g h/mL), half life (T1/2) (1.12 to 1.76 h) and significantly decreased elimination rate constant (Kel ) (0.71 to 0.41 h(-1)), apparent oral clearance (CL/F) (14.58 to 6.48 L/h) of DIC as compared to control. The geometric mean ratios for Cmax, AUC, T1/2, Kel and CL/F of DIC were 1.75, 2.12, 1.65, 0.61 and 0.47, respectively were outside the limits of 0.8-1.25, which indicates clinically significant interaction between DIC and RSV. The results suggest that the altered pharmacokinetics of DIC might be attributed to RSV mediated inhibition of CYP2C9 enzyme. Therefore, combination therapy of DIC along with RSV may represent a novel approach to reduce dosage and results in reduced gastrointestinal side effects of DIC.
authors.affiliation: Drug Metabolism and Clinical Pharmacokinetics Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506009, Telangana State, India.
authors.forename: Satish Kumar
authors.identifier: http://orcid.org/0000-0002-1080-4446
authors.initials: SK
authors.lastname: Bedada
authors.affiliation: Drug Metabolism and Clinical Pharmacokinetics Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506009, Telangana State, India.
authors.forename: Narsimha Reddy
authors.initials: NR
authors.lastname: Yellu
authors.affiliation: Drug Metabolism and Clinical Pharmacokinetics Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506009, Telangana State, India.
authors.forename: Prasad
authors.initials: P
authors.lastname: Neerati
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D065729:Cytochrome P-450 CYP2C9; D004008:Diclofenac / Q000493:pharmacokinetics*; D006207:Half-Life; D064368:Healthy Volunteers; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D010936:Plant Extracts; D013267:Stilbenes; D004008:Diclofenac; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000077185:Resveratrol
keywords: CYP2C9 enzyme; diclofenac; drug-phytochemical interactions; pharmacokinetics; resveratrol