Comparative study on pharmacokinetics of extract from Bufonis venenum and its liposomes

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2024-07-21 DOI:10.1016/j.jpba.2024.116375

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引用次数: 0

Abstract

Bufadienolides and indolealkylamines, the primary active components in Bufonis venenum, have rapid clearance from the body with a short half-life, leading to low bioavailability. Moreover, Bufadienolides and indolealkylamines are associated with serious adverse effects. In order to reduce the toxicities, minimize the adverse effects and simultaneously load lipophilic bufadienolides and hydrophilic indolealkylamines with satisfactory drug loading and encapsulation rate, we prepared Bufonis venenum extract-liposomes (BVE-LP). To compare the pharmacokinetic differences between Bufonis venenum extract (BVE) and its liposomes, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was established to simultaneously detect the 12 chemical components in rat plasma. Results of pharmacokinetic study in SD rats showed that the highest exposure based on the area under the plasma concentration-time curve (AUC_0-t) was obtained by 5-hydroxytryptamine with a mean value of 267.097 μg/L*h in BVE-LP group, which was 72.36 % higher as compared to that obtained in Bufonis venenum extract (BVE) group with a mean value of AUC_0-t of 154.966 μg/L*h. The exposure (AUC_0-t) of desacetylcinobufotalin, desacetylcinobufagin, arenobufagin and telocinobufagin in BVE-LP group was 111.89 %, 94.13 %, 134.08 %, and 92.94 % higher when compared to that in BVE group. With the employment of liposomes, there was an obvious decrease in the clearance of bufotenidine, desacetylcinobufotalin, gamabufotalin, arenobufagin, and telocinobufagin. The terminal half life (t_1/2) of desacetylcinobufotalin, gamabufotalin, arenobufagin, and telocinobufagin in BVE-LP group was increased by 185.96 %, 292.64 %, 196.78 % and 131.29 % when compared to that in BVE group. All the results above indicated that a slower elimination rate and more exposure of some bufadienolides and indolealkylamines was obtained by BVE-LP when compared to BVE group, which verified BVE-LP could provide a therapeutic option for effective delivery of Bufonis venenum in clinical.

Data availability

The data will be shared on reasonable request to the corresponding author.

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布福尼斯提取物及其脂质体的药代动力学比较研究

Bufadienolides 和 indolealkylamines 是 Bufonis venenum 的主要活性成分，它们在体内的清除速度很快，半衰期很短，因此生物利用率很低。此外，布法迪内酯和吲哚烷基胺还会产生严重的不良反应。为了降低毒性，减少不良反应，同时载入亲脂性的布法地尔内酯和亲水性的吲哚烷基胺，并获得满意的载药量和包封率，我们制备了布法地尔提取物-脂质体（BVE-LP）。为了比较布方丹参提取物（BVE）及其脂质体的药代动力学差异，我们建立了超高效液相色谱-串联质谱（UPLC-MS/MS）检测方法，以同时检测大鼠血浆中的 12 种化学成分。对 SD 大鼠进行的药代动力学研究结果表明，根据血浆浓度-时间曲线下面积（AUC0-t）计算，BVE-LP 组的 5-羟色胺暴露量最高，平均值为 267.097 μg/L*h，与 Bufonis venenum 提取物（BVE）组的 AUC0-t 平均值（154.966 μg/L*h）相比，BVE-LP 组的暴露量高出 72.36%。与 BVE 组相比，BVE-LP 组中去乙酰基蟾毒他林、去乙酰基蟾毒黄酮、去乙酰基蟾毒黄酮和去乙酰基蟾毒黄酮的暴露量（AUC0-t）分别高出 111.89 %、94.13 %、134.08 % 和 92.94 %。使用脂质体后，bufotenidine、desacetylcinobufotalin、gamabufotalin、arenobufagin 和 telocinobufagin 的清除率明显下降。与 BVE 组相比，BVE-LP 组的去乙酰西诺布他林、加巴布他林、阿诺巴法金和泰罗西诺布法金的终末半衰期（t1/2）分别延长了 185.96 %、292.64 %、196.78 % 和 131.29 %。所有上述结果表明，与 BVE 组相比，BVE-LP 组的消除速度更慢，一些布法迪内酯和吲哚烷基胺的暴露量更多，这验证了 BVE-LP 可以为布法尼蛇床子素在临床上的有效给药提供一种治疗选择。

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.