Abstract
Objective: The purpose of the present study was to assess the influence ofresveratrol onP-glycoprotein mediated drug disposition in humans using fexofenadine as a P-glycoprotein substrate. Methods: A non-blinded, an open label crossover study was conducted in twelve healthy male volunteers aged between 26 and 31 years. A single dose of fexofenadine hydrochloride 120 mg was given to volunteers during control phase and treatment phases. A single dose of resveratrol 500 mg was given to volunteers once daily for period of 10 days. The blood samples were collected at predetermined time intervals during control and treatment phases. The plasma samples containing fexofenadine hydrochloridewere analyzed by LC-MS/MS. The pharmacokinetic parameters were computed by non-compartmental method and the mean pharmacokinetic parameter differences during control and treatment phases were assessed. Results: Treatment with resveratrol significantly increased thearea under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) offexofenadine to 76.7%(2520.92.48 versus 4454.48 ng.h/mL) and 65.2% (415.08 versus 685.58 ng/mL)respectively when compared to control phase. On other hand, apparentoral clearance (CL/F) and apparent volume of distribution (Vd/F) of fexofenadine were significantly decreased by 42.6% (49.46 versus 28.37 L/h) and 42.1 % (591.73 versus 342.62 L) respectively. However, there was no significant change was observed in T1/2, Kel and Tmaxof fexofenadine upon treatment with resveratrol when compared to control phase. Conclusion: The results of the present study showed that multiple doses of resveratrolenhanced the bioavailability of fexofenadine probably by the inhibition of P-glycoprotein mediated drug efflux in humans.
Highlights
The pharmacokinetic parameters and mean plasma concentration– time profiles of fexofenadine hydrochloride (FEX) after a 10-day treatment with RSV are shown in Table 2 and Figure 1, respectively
The mean area under the plasma concentration-time curve (AUC) of fexofenadine was increased by 76.7% after RSV treatment (2520.92 ± 516.92 versus 4454.48 ± 1238.27 ng·h/mL, P
The 90% confidence intervals (CIs) for the ratio of geometric means (RSV treatment phase:control phase) for AUC, Cmax, CL/F and Vd/F were fell outside the interval (0.8-1.25) but in case T1/2, Tmax and Kel fell within the interval (Table 2) which indicates the interaction between RSV and FEX, the pharmacokinetics of FEX were altered upon RSV treatment
Summary
A non-blinded, an open label crossover study was conducted in twelve healthy male volunteers aged between 26 and 31 years. Twelve healthy male volunteers with an age of 28.17 ± 1.59 (range 26-31) years, weight of 68.3 ± 7.95 (range 52-82) kg, height of 173.2 ± 7.33 (range 165-188) cm and body mass index (BMI) of 22.76 ± 2.02 (range 17.99-24.95) were participated in the study (Table 1). All participants gave their written informedconsent prior to the study. The subjects were instructed toabstain from taking any medication for at least 2 weeks priorto and during the study period. All the subjects were asked toabstain from alcohol, caffeine-containing beverages, tea andfruit juices during the study period
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
