{"title":"Comparative study on pharmacokinetics of extract from Bufonis venenum and its liposomes","authors":"","doi":"10.1016/j.jpba.2024.116375","DOIUrl":null,"url":null,"abstract":"<div><p>Bufadienolides and indolealkylamines, the primary active components in <em>Bufonis venenum</em>, 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 <em>Bufonis venenum</em> extract-liposomes (BVE-LP). To compare the pharmacokinetic differences between <em>Bufonis venenum</em> 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<sub>0-t</sub>) 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 <em>Bufonis venenum</em> extract (BVE) group with a mean value of AUC<sub>0-t</sub> of 154.966 μg/L*h. The exposure (AUC<sub>0-t</sub>) 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<sub>1/2</sub>) 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 <em>Bufonis venenum</em> in clinical.</p></div><div><h3>Data availability</h3><p>The data will be shared on reasonable request to the corresponding author.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmaceutical and biomedical analysis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0731708524004151","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
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 (AUC0-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 AUC0-t of 154.966 μg/L*h. The exposure (AUC0-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 (t1/2) 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.
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.