Rachana S Bhimanwar, Lata P Kothapalli, Akshay Khawshi
{"title":"Evaluation of Quercetin's Bioenhancing Effect on Oral Pharmacokinetics of Rosuvastatin in Wistar Rats Using RP-HPLC Method.","authors":"Rachana S Bhimanwar, Lata P Kothapalli, Akshay Khawshi","doi":"10.2174/0118715257258735231016112348","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The absolute oral bioavailability of rosuvastatin (RST), a secondgeneration statin, is low i.e. 20% and only 10% is recovered as metabolite N-desmethy l rosuvistatin. Since it is a hydrophilic statin, RST relies on the organic anion transporting polypeptide- 1B1 (OATP-1B1), as the key mechanism for active transport into hepatocytes. Quercetin (QUE) being a bio enhancer and inhibitor of OATP1B1 can augment the bioavailability and pharmacokinetics of RST.</p><p><strong>Objectives: </strong>The present study includes the development of a simple and validated bioanalytical Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the estimation of RST and to study the effect of co-administration of QUE as a bio enhancer on its bioavailability.</p><p><strong>Methods: </strong>An analytical column of Kromasil 100, C18 (250 mm × 4.6 mm, 5 μm), was used for chromatographic separationand acetonitrile (ACN): acetic acid buffer pH 3.0 adjusted with glacial acetic acid (55:45 Vol. %) as mobile phase with flow rate 1.0 ml/min monitored at 242 nm. The ACN: methanol (50:50 Vol. %) was employed as the final solvent for extraction. The developed method has been successfully applied in a study on the pharmacokinetics of the drug RST in rats after co-administration of QUE, which was carried out using non-compartmental analysis in order to estimate the blood concentration of the drug.</p><p><strong>Results: </strong>The pharmacokinetics of RST was found to be altered significantly (highest concentration of RST in the blood (<i>C</i><sub>max</sub>) = 67.3 ng/ml to 122.2 ng/ml) (p < 0.001), area under curve (AUC)<sub>0-t</sub> (p < 0.0001) and AUC<sub>0-inf</sub> (p = 0.0005) when co-administered with QUE at 120 min (<i>t</i><sub>max</sub>).</p><p><strong>Conclusion: </strong>The results are in accordance with the fact that QUE increases plasma levels in rats through herb-drug interactions.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":"22 4","pages":"456-465"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular & hematological agents in medicinal chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118715257258735231016112348","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The absolute oral bioavailability of rosuvastatin (RST), a secondgeneration statin, is low i.e. 20% and only 10% is recovered as metabolite N-desmethy l rosuvistatin. Since it is a hydrophilic statin, RST relies on the organic anion transporting polypeptide- 1B1 (OATP-1B1), as the key mechanism for active transport into hepatocytes. Quercetin (QUE) being a bio enhancer and inhibitor of OATP1B1 can augment the bioavailability and pharmacokinetics of RST.
Objectives: The present study includes the development of a simple and validated bioanalytical Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the estimation of RST and to study the effect of co-administration of QUE as a bio enhancer on its bioavailability.
Methods: An analytical column of Kromasil 100, C18 (250 mm × 4.6 mm, 5 μm), was used for chromatographic separationand acetonitrile (ACN): acetic acid buffer pH 3.0 adjusted with glacial acetic acid (55:45 Vol. %) as mobile phase with flow rate 1.0 ml/min monitored at 242 nm. The ACN: methanol (50:50 Vol. %) was employed as the final solvent for extraction. The developed method has been successfully applied in a study on the pharmacokinetics of the drug RST in rats after co-administration of QUE, which was carried out using non-compartmental analysis in order to estimate the blood concentration of the drug.
Results: The pharmacokinetics of RST was found to be altered significantly (highest concentration of RST in the blood (Cmax) = 67.3 ng/ml to 122.2 ng/ml) (p < 0.001), area under curve (AUC)0-t (p < 0.0001) and AUC0-inf (p = 0.0005) when co-administered with QUE at 120 min (tmax).
Conclusion: The results are in accordance with the fact that QUE increases plasma levels in rats through herb-drug interactions.
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