Author(s): Mohammed Abdul Aziz Shahid, Y Shravan Kumar, Syed Umar Farooq, Md. Shamim Qureshi

Email(s): shahiduz_zama@yahoo.co.in

DOI: 10.5958/0974-360X.2020.00301.7   

Address: Mohammed Abdul Aziz Shahid1*, Y Shravan Kumar2, Syed Umar Farooq3, Md. Shamim Qureshi4
1Research Scholar, Department of Pharmacology, Singhania University, Pacheri Bari, Jhun Jhunu, Rajasthan.
2Professor, Department of Pharmaceutics, Vagdevi College of Pharmacy, Warangal, Telangana.
3Research Scholar, Department of Pharmaceutics, Singhania University, Pacheri Bari, Jhun Jhunu, Rajasthan.
4Anwarul Uloom College of Pharmacy, New Mallepally, Hyderabad, Telangana – 500001.
*Corresponding Author

Published In:   Volume - 13,      Issue - 4,     Year - 2020


ABSTRACT:
The present study aimed to assess the effect of resveratrol on the intestinal transport and oral bioavailability of carvedilol in rats. The intestinal transport was evaluated by in vitro non-everted intestinal sac The present study aimed to assess the effect of resveratrol on the intestinal transport and oral bioavailability of carvedilol in rats. The intestinal transport was evaluated by in vitro non-everted intestinal sac method. The oral pharmacokinetics was evaluated by conducting oral bioavailability study. In both methods the rats were pretreated with resveratrol for 7 days. In intestinal sac method rats were sacrificed by using anesthetic ether. The intestinal segments were isolated and used for the studies. The probe drug (carvedilol) solution was placed in the isolated intestinal sac. Samples were collected at preset time points and replaced with fresh buffer. The drug content in the samples was estimated using high performance liquid chromatography method. Control experiments were also performed. A significant increase in transport of carvedilol in duodenum, jejunum and ileum was seen with resveratrol treated group when compared to control. In oral bioavailability study the pharmacokinetic parameters like area under plasma concentration time curve and peak plasma concentration of carvedilol increased significantly in resveratrol treated group from control group. These results suggest that resveratrol increased the intestinal transport and oral bioavailability due to inhibition of P-gp mediated efflux in the intestine. Further studies are recommended to prove this effect in human beings (p<0.05) difference compared to control, in the transport of carvedilol from the intestinal sacs which were pretreated with resveratrol. It suggests that resveratrol might be acting by inhibiting the transporters and enzymes which are responsible for transport/metabolism of carvedilol. From the results it can be concluded that resveratrol be acting by inhibiting p-glycoprotein as carvedilol is transported by p-glycoprotein. Further studies are recommended to prove their effects in human beings.


Cite this article:
Mohammed Abdul Aziz Shahid, Y Shravan Kumar, Syed Umar Farooq, Md. Shamim Qureshi. Effect of Resveratrol Pretreatment on Intestinal Transport and Oral Bioavailability of Carvedilol in Rats by P-gp Inhibition. Research J. Pharm. and Tech. 2020; 13(4):1660-1664. doi: 10.5958/0974-360X.2020.00301.7

Cite(Electronic):
Mohammed Abdul Aziz Shahid, Y Shravan Kumar, Syed Umar Farooq, Md. Shamim Qureshi. Effect of Resveratrol Pretreatment on Intestinal Transport and Oral Bioavailability of Carvedilol in Rats by P-gp Inhibition. Research J. Pharm. and Tech. 2020; 13(4):1660-1664. doi: 10.5958/0974-360X.2020.00301.7   Available on: https://rjptonline.org/AbstractView.aspx?PID=2020-13-4-11


REFERENCES:
1.    Cullington D, Yassin A, and Cleland J. Betablockers in the treatment of cardiovascular disease Prescriber. 2008; 19: 31–39.
2.    Lainscak M et al. Treatment of chronic heart failure with carvedilol in daily practice: the SATELLITE survey experience. Int J Cardiol. 2007; 122: 149–155.
3.    Morgan T. Clinical pharmacokinetics and pharmacodynamics of carvedilol. Clin Pharmacokinet. 1994; 26: 335–346.
4.    Phuong NT et al. Enantioselective pharmacokinetics of carvedilol in human volunteers. Arch Pharm Res. 2004; 27: 973–977.
5.    Oldham HG, and Clarke SE. In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)- carvedilol. Drug Metab Dispos 1997; 25: 970–977.
6.    Ishida K et al. Stereoselective oxidation and glucuronidation of carvedilol in human liver and intestinal microsomes. Biol Pharm Bull. 2008; 31: 1297–1300.
7.    Kalantari H, and Das DK. Physiological effects of resveratrol. Biofactors. 2010; 36: 401–406.
8.    Brisdelli F, D’Andrea G,  and Bozzi A. Resveratrol: a natural polyphenolwith multiple chemopreventive properties. Curr DrugMetab. 2009; 10: 530–546.
9.    Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: amoleculewhose time has come? And gone?. Clin Biochem. 1997; 30: 91–113.
10.    Romano B et al. Novel insights into the pharmacology of flavonoids. Phytother Res. 2013; 27: 1588–1596.
11.    Nabekura T, Kamiyama S, and Kitagawa S. Effects of dietary chemopreventive phytochemicals on P-glycoprotein function. Biochem Biophys Res Commun. 2005; 327: 866–870.
12.    Ruan et al. Prediction of human absorption of natural compounds by the non-everted rat intestinal sac model. Eur. J. Med. Chem. 2006;  41: 605-610.
13.    Benet LZ, Cummins CL, and Wu CY. Transporter-enzyme interactions: Implications for predicting drug–drug interactions from in vitro data. Curr Drug Metab. 2003; 4:393–398.
14.    Cummins CL, Jacobsen W, and Benet LZ. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP 3A4. J PharmacolExpTher. 2002; 300:1036–1045.
15.    Genty M, Gonzalez G. Determination of the passive absorption through the rat intestine using chromatographics indices and molar volume. Eur. J. Pharm. Sci. 2001; 12: 223-229.
16.    Kaul, S. and Ritschel W.A. Studies of the intestinal transfer of coumarin and 7-hydroxycoumarin across guinea pig and rat small intestine. Arzneim. Forsch. 1981; 31: 790-795.
17.    Kivisto K T, Lamberg T S, and Neuvonen P J. Interactions of buspirone with traconazole and rifampicin: effects on the pharmacokinetics of the active 1-(2-pyrimidinyl)-piperazine metabolite of buspirone. Pharmacol Toxicol. 1999; 84: 94-97.
18.    Chan WK, Delucchi AB. Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4. Life Sci 2000; 67: 3103–3112.
19.    Piver B, Berthou F, Dreano Y, Lucas D. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett. 2001; 125: 83–91.
20.    Piver B, Berthou F, Dreano Y, Lucas D. 2001. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett. 2001; 125: 83–91.
21.    Choi Jun-Shik, Choi Byung-Chul, and Kang KeonWook. Effect of resveratrol on the pharmacokinetics of oral and intravenous nicardipine in rats: possible role of P-glycoprotein inhibition by resveratrol. Pharmazie. 2009; 64: 49–52.
22.     Hong Soon-Pyo,Choi Dong-Hyun, Choi Jun-Shik. Effects of Resveratrol on the Pharmacokinetics of Diltiazem and Its Major Metabolite, Desacetyldiltiazem, in Rats. Cardiovasc Ther. 2008; 26: 269-275.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

1.3
2021CiteScore
 
56th percentile
Powered by  Scopus


SCImago Journal & Country Rank

Journal Policies & Information


Recent Articles




Tags


Not Available