| 摘要: |
| 【目的】研制阿德呋啉-β-环糊精包合物(阿德呋啉-β-CD)，探讨其在鸡体内的药动学特征。【方法】以溶液搅拌法制备阿德呋啉-β-CD包合物；以β-CD与阿德呋啉物质的量比、包合温度、冰醋酸与水的体积比和搅拌时间为影响因素，以综合评分（包合率和增溶倍数之和）为指标，通过正交试验优化制备条件；采用紫外光谱、薄层色谱和相溶解度法对制备的包合物进行验证。将10只试验鸡均分为2组，分别单次口服8 mg/kg阿德呋啉和阿德呋啉-β-CD包合物，采用液相色谱-串联质谱(HPLC-MS/MS)方法检测不同时间点的血药质量浓度，用3p97药代计算程序进行分析，计算主要药代动力学参数。【结果】阿德呋啉经包合作用形成了新的物相，优选的阿德呋啉-β-CD制备工艺为：β-CD与阿德呋啉物质的量比为1.5∶1，搅拌时间为8 h，冰醋酸与水体积比为2∶8，包合温度为65 ℃。阿德呋啉-β-CD包合物在鸡体内的药动学特征符合口服吸收二室模型，其主要药代动力学参数峰质量浓度（Cmax）为(246.76±17.88) ng/mL，达峰时间（T(peak)）为(0.312±0.004) h，曲线下面积（AUC）为(1 614.91±1.232) (ng·h)/mL，相对生物利用度(F)为146.4%。【结论】成功制备了阿德呋啉-β-CD包合物，其在鸡体内达峰时间缩短，峰质量浓度提高，表明包合后阿德呋啉在鸡体内的吸收速度、程度和生物利用度均提高。 |
| 关键词: 阿德呋啉 β-环糊精 包合物 鸡 HPLS-MS/MS 药代动力学 |
| DOI： |
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| 基金项目:安徽省教育厅重点项目“高效低毒抗球虫新兽药的研发”(KJ2012A115) |
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| Preparation of adprin-β-cyclodextrin inclusion complex and its pharmacokinetics in chicken |
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SU Ting-ting,RUAN Xiang-chun,ZHOU Fei-ya,et al
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| Abstract: |
| 【Objective】The aim of this study was to prepare the inclusion complex of adprin-β-cyclodextrin and evaluate its pharmacokinetic behavior in chicken.【Method】Adprin-β-cyclodextrin inclusion complex was prepared using solution-stirring method.The influence factors were ratio of the amount of substance,temperature,volume ratio of acetic acid to water,and mixing time.The best preparation method was determined by orthogonal test using comprehensive score (sum of inclusion rate and solubilization ratio) as index.The identification of the inclusion complex was carried out by ultraviolet spectra,thin layer chromatography,and phase solubility method.The blood samples from 10 chickens fed with a single dose of either adprin or adprin-β-CD inclusion complex solusion were collected to measure adprin concentrations in plasma by HPLC-MS/MS.The pharmacokinetic parameters were analyzed with 3p97 software.【Result】The inclusion complex was successfully prepared.The optimum preparation conditions were:molar ratio of β-cyclodextrin to adprin 1.5∶1,ratio of glacial acetic acid to water 2∶8,inclusion temperature 65 ℃,and time 8 h.The major pharmacokinetic parameters of adprin-β-cyclodextrin were:Cmax (246.76±17.88) ng/mL,T(peak) (0.312±0.004) h,and AUC (1 614.91±1.232) (ng·h)/mL,and relative bioavailability of adprin-β-cyclodextrin 146.4%.【Conclusion】Adprin-β-CD inclusion complex was prepared successfully,and it could significantly improve the solubility bioavailability of adprin in chicken. |
| Key words: adprin β-cyclodextrin inclusion complex chicken HPLS MS/MS pharmacokinetics |
