Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India.
Cardiovasc Hematol Agents Med Chem. 2024;22(4):456-465. doi: 10.2174/0118715257258735231016112348.
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.
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.
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.
The pharmacokinetics of RST was found to be altered significantly (highest concentration of RST in the blood () = 67.3 ng/ml to 122.2 ng/ml) (p < 0.001), area under curve (AUC) (p < 0.0001) and AUC (p = 0.0005) when co-administered with QUE at 120 min ().
The results are in accordance with the fact that QUE increases plasma levels in rats through herb-drug interactions.
瑞舒伐他汀（RST）是一种第二代他汀类药物，其绝对口服生物利用度较低，即 20%，只有 10% 以代谢物 N-去甲瑞舒伐他汀的形式回收。由于它是一种亲水性他汀类药物，RST 依赖有机阴离子转运多肽 1B1（OATP-1B1）作为主动转运进入肝细胞的关键机制。槲皮素（QUE）作为 OATP1B1 的生物增强剂和抑制剂，可以增加 RST 的生物利用度和药代动力学。
本研究包括开发一种简单且经过验证的反相高效液相色谱（RP-HPLC）生物分析方法来估算 RST，并研究 QUE 作为生物增强剂共同给药对其生物利用度的影响。
采用 Kromasil 100，C18（250mm×4.6mm，5μm）分析柱进行色谱分离，以乙腈（ACN）：用冰醋酸调节 pH 值为 3.0 的醋酸缓冲液（55:45 Vol.％）作为流动相，流速为 1.0ml/min，在 242nm 处检测。ACN：甲醇（50:50 Vol.％）作为最终提取溶剂。该方法已成功应用于 QUE 共同给药后大鼠体内 RST 药代动力学的研究，采用非房室分析方法估算药物的血药浓度。
发现 RST 的药代动力学发生了显著变化（血液中 RST 的最高浓度（）= 67.3ng/ml 至 122.2ng/ml）（p <0.001），曲线下面积（AUC）（p <0.0001）和 AUC（p = 0.0005）当与 QUE 在 120 分钟时共同给药时（）。
结果与 QUE 通过草药-药物相互作用增加大鼠血浆水平的事实一致。
