| 王晨,许明哲,胡昌勤.利用计算机模拟技术对头孢克肟口服固体制剂有效性的研究与评价[J].中国药事,2019,33(11):1270-1279 |
| 利用计算机模拟技术对头孢克肟口服固体制剂有效性的研究与评价 |
| On Effectiveness of Cefixime Oral Solid Preparations by Computer Simulation |
| 投稿时间：2019-07-09 |
| DOI：10.16153/j.1002-7777.2019.11.010 |
| 中文关键词: 头孢克肟 生理药代动力学 有效性 药代动力学 吸收 分布 代谢 排泄 |
| 英文关键词: cefixime physiologically based pharmacokinetics effectiveness pharmacokinetics absorption distribution metabolism excretion |
| 基金项目:国家“重大新药创制”科技重大专项资助项目（编号2017ZX09101001） |
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| 中文摘要: |
| 目的：本研究建立了一种头孢克肟口服固体制剂通用型有效性评价方法。方法：通过对品种结构、理化性质、药代动力学特征和生物药剂学参数的研究和确证，结合静脉注射、口服等不同给药途径在比格犬及人类等不同种属中的药时曲线数据，建立并验证人口服头孢克肟的生理药代动力学模型，以此模拟口服头孢克肟在人体内的吸收、分布、代谢、消除过程，拟合药物的累计吸收曲线，作为品种口服固体制剂溶出曲线的评价依据。结果：通过对不同规格片剂、分散片、胶囊、颗粒剂和混悬剂的体内数据的验证比较，证实该模型应用的适用性和准确性。结论：本研究建立的有效性评价方法，能够明确溶出度行为与药物在体内吸收的关系，提高体外有效性评价的可靠性和准确度，可大幅度降低仿制药评价的过程成本。 |
| 英文摘要: |
| Objective:To establish a general-purpose method to evaluate the effectiveness of cefixime oral solid preparations. Methods:The structure, physical and chemical properties, pharmacokinetic characteristics, and biopharmaceutic parameters of cefixime oral solid preparations were studied and verified. These data were combined with concentration-time curve data of intravenous, oral and other different routes of administration experimented in different species, such as beagle dogs and humans, to establish and validate a physiologically based pharmacokinetic model for cefixime orally administrated in humans. This model was used to simulate the absorption, distribution, metabolism, and excretion of cefixime orally administrated in humans. Additionally, the model was fitted to the cumulative-absorption curve of cefixime, and therefore was served as a basis for assessing the dissolution curves of oral solid preparations of different moieties. Results:The applicability and accuracy of this model were confirmed through validation and comparison of in vivo data of tablets, dispersible tablets, capsules, granules, and suspensions of different specifications. Conclusion:The effectiveness evaluation method established in this study can clarify the connection between dissolution behavior and drug absorption in vivo, so as to improve the reliability and accuracy of in vitro efficacy evaluation, and greatly reduce the process cost of generic drug evaluation. |
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