| 摘要: |
| 为建立犬用药物生物药剂学分类系统(BCS)，采用直肠测温法和pH原位测量法对犬胃肠道(GI)生理参数进行了测定，并建立溶解度检测条件；应用在体原位肠灌注技术建立药物渗透性检测方法，并对7种模型药物的溶解度和渗透性进行测定及分类。结果表明:1)药物溶解度的测定条件为最高单剂量药物可完全溶解在38.5 ℃，pH 3.0~8.0范围内的水性缓冲液中；2)Do计算结果显示氨苄西林、林可霉素和盐酸洛美沙星被分类为高溶解度药物，阿莫西林、多西环素和地高辛被分类为低溶解度药物；3)美托洛尔在十二指肠、空肠和回肠中的有效渗透率(Peff)分别为1.45×10-4、1.05×10-4和1.18×10-4 cm/s，其吸收分数(Fa)均大于85 %且不受pH影响，表明该药物可作为渗透性分类的边界性药物；4)根据溶解度与渗透性测量结果对7种模型药物进行BCS分类，其中美托洛尔被分为1类，多西环素和地高辛被分为2类，氨苄西林、林可霉素和盐酸洛美沙星被分为3类，阿莫西林被分为4类。综上，本研究初步确定了犬用药物溶解度测定条件及渗透性测定方法，为犬用药物BCS分类系统的建立提供了数据支撑。 |
| 关键词: 生物药剂学分类系统 犬 溶解度 渗透性 美托洛尔 |
| DOI：10.11841/j.issn.1007-4333.2022.07.14 |
| 投稿时间：2021-05-14 |
| 基金项目:十三五国家重点研发计划(2016YFD0501309) |
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| Preliminary establishment of canine biopharmaceutical classification system |
|
WANG Cuncai1,LI Kang2,HAO Zhihui1*
|
| (1.College of Veterinary Medicine/Center for Research and Development of Chinese Traditional Veterinary Medicine, China Agricultural University, Beijing 100193, China;2.Agricultural Biopharmaceutical Laboratory of Qingdao Agricultural University, Qingdao 266109, China) |
| Abstract: |
| In order to establish the canine drug biopharmaceutical classification system(BCS), the physiological parameters of canine gastrointestinal tract(GI)were measured by rectal temperature measurement and in-situ pH measurement methods, and the solubility test conditions were established. The in-situ intestinal perfusion technique was used to establish the drug permeability detection method, and the solubility and permeability of seven model drugs were determined and classified. The results showed that: 1)The determination condition of drug solubility is that the highest single-dose drug can be completely dissolved in aqueous buffer within the range of pH 3. 0-8. 0 at 38. 5 ℃. 2)The Do calculation results showed that ampicillin, lincomycin and lomefloxacin hydrochloride were classified as high solubility drugs, while amoxicillin, doxycycline and digoxin were classified as low solubility drugs. 3)The effective permeability(Peff)of metoprolol in the duodenum, jejunum and ileum were 1. 45×10-4, 1. 05×10-4 and 1. 18×10-4 cm/s, respectively. And their absorption fractions(Fa)were all greater than 85 % and were not affected by pH, indicating that the drug can be used as the boundary of permeability classification. 4)According to the measurement results of solubility and permeability, seven model drugs were classified by BCS. Metoprolol was divided into Class 1, doxycycline and digoxin were divided into Class 2, ampicillin, lincomycin and lomefloxacin hydrochloride were divided into Class 3, and amoxicillin was divided into Class 4. In conclusion, this study preliminarily determined the conditions for the determination of solubility and permeability of canine drugs, and provided data support for the establishment of BCS classification system for canine drugs. |
| Key words: biopharmaceutics classification system dogs solubility permeability metoprolol |
