Cerqueira Cássia, Santos Valdeene, Araújo Jackeline, Pereira Laiz, Batista Fabiana, Soares Denis, Azeredo Francine, Ferreira Ederlan
School of Pharmacy, Federal University of Bahia, Barão de Jeremoabo Street, Salvador 40170-115, Brazil.
Center for Pharmacometrics & System Pharmacology, College of Pharmacy, University of Florida, Orlando, FL 32610, USA.
Nutrients. 2025 Jan 3;17(1):181. doi: 10.3390/nu17010181.
Studies have demonstrated that resveratrol exerts several pharmacological effects. However, the pharmacokinetic parameters are not completely established. This study describes the plasma pharmacokinetics and tissue distribution of resveratrol after administration by different routes and doses in rats. A reliable, simple, and sensitive HPLC method using UV detection for the quantification of resveratrol in rat plasma and tissues was developed and validated. In addition, a pharmacokinetic analysis using non-compartmental and population modeling was performed. The pharmacokinetic parameters of resveratrol after the administration of 5 mg/kg via i.v. bolus calculated by non-compartmental analysis were a constant of elimination (ke) of 0.09 h ± 0.04, a half-life (t1/2) of 9.5 h ± 3.7, an apparent volume of distribution (Vd) of 5.8 L/kg ± 4.7, a clearance (Cl) of 0.39 L/h/Kg ± 0.26, and an area under the curve (AUC) of 6076 ng/h/mL ± 2959. The results obtained after the administration of 100 mg/kg p.o. were an elimination constant (ke) of 0.12 ± 0.07 h, a half-life (t1/2) of 7.9 ± 4.2 h, the apparent volume distribution (Vd) of 13.3 ± 3.3 L/kg, a clearance (Cl) of 1.76 ± 0.49 L/h/Kg ± 0.26, and an area under the curve (AUC) of 6519 ± 1592 ng/h/mL. For the tissue distribution analysis, 10 mg/kg of resveratrol was intravenously administered to rats and the molecule was quantified in the liver, lung, kidney, heart, stomach, spleen, adipose tissue, and brain of the animals. The population pharmacokinetic modeling showed that resveratrol has a two-compartment model in both routes of administration and has a higher volume of distribution when it is given orally. In addition, resveratrol showed a high brain concentration after iv administration, which indicates that this molecule is capable of crossing the blood-brain barrier of animals, a crucial capacity for its neuroprotective activity.
研究表明，白藜芦醇具有多种药理作用。然而，其药代动力学参数尚未完全确定。本研究描述了大鼠经不同途径和剂量给药后白藜芦醇的血浆药代动力学和组织分布情况。开发并验证了一种可靠、简单且灵敏的高效液相色谱法，该方法采用紫外检测对大鼠血浆和组织中的白藜芦醇进行定量。此外，还进行了非房室和群体建模的药代动力学分析。通过非房室分析计算，静脉推注5 mg/kg白藜芦醇后的药代动力学参数为：消除常数（ke）为0.09 h±0.04，半衰期（t1/2）为9.5 h±3.7，表观分布容积（Vd）为5.8 L/kg±4.7，清除率（Cl）为0.39 L/h/Kg±0.26，曲线下面积（AUC）为6076 ng/h/mL±2959。口服100 mg/kg后的结果为：消除常数（ke）为0.12±0.07 h，半衰期（t1/2）为7.9±4.2 h，表观分布容积（Vd）为13.3±3.3 L/kg，清除率（Cl）为1.76±0.49 L/h/Kg±0.26，曲线下面积（AUC）为6519±1592 ng/h/mL。对于组织分布分析，向大鼠静脉注射10 mg/kg白藜芦醇，并对动物的肝脏、肺、肾、心脏、胃、脾脏、脂肪组织和大脑中的该分子进行定量。群体药代动力学建模表明，白藜芦醇在两种给药途径中均具有二室模型，且口服时分布容积更大。此外，静脉注射后白藜芦醇在脑中的浓度较高，这表明该分子能够穿过动物的血脑屏障，这对其神经保护活性至关重要。
