Pharmacokinetic interaction study between quercetin and valsartan in rats and in vitro models.

Abstract

Valsartan is a potent, orally active non-peptide tetrazole derivative and selectively inhibits angiotensin II receptor type 1 which causes reduction in blood pressure and is used in treatment of hypertension. The risk of heart disease mortality decreased significantly as flavonoid intake increased. Interestingly, the flavonoid-containing foods contain a high amount of Quercetin. The objective of this study was to evaluate the influence of quercetin on the pharmacokinetics of valsartan. In vivo studies were performed on rats. Rats were treated with quercetin (10 mg/kg) and valsartan (10 mg/kg), blood samples were collected at 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 and 8 h. Plasma concentration of valsartan was estimated by Reverse Phase (RP-HPLC). Quercetin significantly increases the plasma concentration of valsartan and peak concentration (70.45 µg/mL) was achieved at 3.5 h. In vitro studies were performed on rat intestinal everted sacs. The transport of valsartan from serosal side to mucosal side decreased from 53.12 ± 1.27 to 40.15 ± 0.45 µg/mL in the presence of quercetin and from 53.12 ± 1.27 to 28.68 ± 0.31 µg/mL in the presence of verapamil (standard P-glycoprotein (P-gp) inhibitor) at 120 min. Verapamil is a potent P-gp and CYP3A4 inhibitor. Quercetin is a P-gp inhibitor and may be an inhibitor of CYP3A4. The simultaneous administration of quercetin significantly increases the intestinal absorption and decreases the efflux of valsartan. The observed effect may be beneficial to develop oral valsartan dosage forms using safe P-gp inhibitor (quercetin) to improve its oral bioavailability.

• Authors: Venkatesh R Challa, P Ravindra Babu, Siva R Challa, Benito Johnson, C Maheswari
• Journal: Drug development and industrial pharmacy (Drug Dev Ind Pharm) Vol. 39 Issue 6 Pg. 865-72 (Jun 2013) ISSN: 1520-5762 [Electronic] England
• PMID: 22670860 (Publication Type: Journal Article)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antioxidants
• Tetrazoles
• Valsartan
• Quercetin
• Valine

Topics

• Angiotensin II Type 1 Receptor Blockers (blood, pharmacology)
• Animals
• Antioxidants (metabolism, pharmacology)
• Drug Interactions (physiology)
• Intestinal Absorption (drug effects, physiology)
• Male
• Organ Culture Techniques
• Quercetin (blood, pharmacology)
• Random Allocation
• Rats
• Rats, Wistar
• Tetrazoles (blood, pharmacology)
• Valine (analogs & derivatives, blood, pharmacology)
• Valsartan