Abstract

Context

Laurolitsine is an aporphine alkaloid and exhibits potent antihyperglycemic and antihyperlipidemic effects in ob/ob mice.

Objective

To investigate the pharmacokinetics, tissue distribution and excretion of laurolitsine.

Materials and methods

A LC-MS/MS method was established and validated to determine laurolitsine concentrations in the biological matrix of rats (plasma, tissue homogenate, urine and faeces). 10 Sprague-Dawley (SD) rats were used for plasma exposure study: 5 rats were injected with 2.0 mg/kg of laurolitsine via the tail vein, and the other 5 rats were administered laurolitsine (10.0 mg/kg) by gavage. 25 SD rats used for tissue distribution study and 5 SD rats for urine and faeces excretion study: rats administered laurolitsine (10.0 mg/kg) by gavage. After administered, serial blood, tissue, urine and faeces were collected. Analytical quantification was performed by a previous LC-MS/MS method. The pharmacokinetics, bioavailability, tissue distribution and excretion of laurolitsine were described.

Results

The pharmacokinetic parameters of oral and intravenous administration with T_max were 0.47 and 0.083 h, t_1/2 were 3.73 and 1.67 h, respectively. Oral bioavailability was as low as 18.17%. Laurolitsine was found at a high concentration in the gastrointestinal tract, liver, lungs and kidneys (26 015.33, 905.12, 442.32 and 214.99 ng/g at 0.5 h, respectively) and low excretion to parent laurolitsine in urine and faeces (0.03 and 1.20% in 36 h, respectively).

Conclusions

This study established a simple, rapid and accurate LC-MS/MS method to determine laurolitsine in different rat samples and successful application in a pharmacokinetic study.

中文翻译：

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Sprague-Dawley大鼠山茱萸中月桂石碱的药代动力学、组织分布及排泄研究

摘要

语境

Laurolitsine 是一种阿朴啡生物碱，在 ob/ob 小鼠中表现出有效的抗高血糖和抗高血脂作用。

客观的

研究月桂酸的药代动力学、组织分布和排泄。

材料和方法

建立并验证了 LC-MS/MS 方法以确定大鼠生物基质（血浆、组织匀浆、尿液和粪便）中的月桂酸浓度。10 只 Sprague-Dawley (SD) 大鼠用于血浆暴露研究：5 只大鼠通过尾静脉注射 2.0 mg/kg 月桂石碱，另外 5 只大鼠通过管饲法给药月桂石碱 (10.0 mg/kg)。用于组织分布研究的 25 只 SD 大鼠和用于尿液和粪便排泄研究的 5 只 SD 大鼠：通过管饲法给大鼠施用月桂酸钙 (10.0 mg/kg)。给药后，收集系列血液、组织、尿液和粪便。分析定量是通过以前的 LC-MS/MS 方法进行的。描述了月桂酸的药代动力学、生物利用度、组织分布和排泄。

结果

口服和静脉内给药的药物动力学参数与Ť_最大值 分别为0.47和0.083小时，吨_1/2分别为3.73和1.67小时，分别。口服生物利用度低至 18.17%。在胃肠道、肝脏、肺和肾脏中发现了高浓度的月桂酸（在 0.5 小时时分别为 26 015.33、905.12、442.32 和 214.99 ng/g）并且在尿液和粪便中向母体月桂酸的排泄量低（0.03% 和 1.03%）分别在 36 小时内）。

结论

本研究建立了一种简单、快速、准确的 LC-MS/MS 方法来测定不同大鼠样品中的月桂酸，并成功应用于药代动力学研究。