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.

Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers

“…In this study, our results are consistent with previous studies, where an increased C max , AUC, and t 1/2 with decreased k el and CL/F were found for DIC in humans after administration of diosmin (Rajnarayana et al, ), resveratrol (Bedada, Yellu et al, ), and piperine (Bedada, Kotakonda et al, ), and the observed effects are most likely the results of inhibition of CYP2C9 enzyme. It has been reported that quercetin inhibited CYP2C9‐mediated DIC 4′‐hydroxylation in human liver microsomes (Rastogi & Jana, ; Si et al, ).…”

“…As a CYP2C9 substrate, DIC has the potential to interact with various inhibitors and inducers of CYP2C9 enzyme. Several drugs (Hynninen et al, ; Kovarik et al, ; Pedrazzoli Júnior et al, ) and herbal constituents (Bedada, Boga, & Kotakonda, ; Bedada, Yellu, & Neerati, ; Rajnarayana et al, ) altered the pharmacokinetics of DIC due to modulation of CYP2C9 enzyme in humans.…”

“…Several drugs (Hynninen et al, 2007;Kovarik et al, 1996;Pedrazzoli Júnior et al, 1997) and herbal constituents (Bedada, Boga, & Kotakonda, 2017;Bedada, Yellu, & Neerati, 2016;Rajnarayana et al, 2007) altered the pharmacokinetics of DIC due to modulation of CYP2C9 enzyme in humans.…”

Resveratrol in the foodomics era: 1:25,000

“…Human studies dealing with the pharmacokinetics and metabolism of resveratrol have so far been limited to small cohorts, often including fewer than 50 individuals . The majority of the studies have been conducted to test its effect in single cell lines and in animal models, normally with a deductive focus on predefined hypotheses and/or findings .…”

Recent studies on resveratrol and its biological and pharmacological activity

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