摘要
目的评价美沙拉嗪肠溶缓释颗粒剂体内药物代谢动力学,通过与市售制剂的药动学特征比较,阐述美沙拉嗪肠溶缓释颗粒剂的临床前药代动力学特征,为新药评价提供可靠依据。方法以单剂量和多剂量2种方式口服给药,选取比格犬为受试对象,采用LC-MS/MS法测定血浆样品药物浓度。通过药动学参数估算和统计分析,评价美沙拉嗪肠溶缓释颗粒剂的体内吸收和消除过程、相对生物利用度、体内蓄积效应以及与市售制剂的药动学特征进行比较。结果美沙拉嗪肠溶缓释颗粒剂在比格犬体内单剂量口服(灌胃)给药后,美沙拉嗪缓释颗粒剂和美沙拉嗪肠溶片以美沙拉嗪表征的相对生物利用度分别为101.30%±20.20%、109.20%±30.80%。多剂量口服(灌胃)给药后,体内无蓄积效应。通过相对生物利用度和药代动力学参数的统计分析比较研究,提示美沙拉嗪肠溶缓释颗粒剂与市售的2种制剂无显著性差异。结论美沙拉嗪肠溶缓释颗粒剂吸收和消除过程基本呈线性动力学特征,多剂量给药后5 d左右达稳态、体内无蓄积,药动学参数与市售制剂无显著性差异。
Objective To evaluate the pharmacokinetics of mesalazine enteric sustained-release granules in vivo.By comparing with the pharmacokinetic characteristics of the commercial preparations,the pre-clinical pharmacokinetic characteristics of mesalazine enteric sustained-release granules were described,in order to provide a reliable basis for the evaluation of new drugs.Methods Single dose and multi dose oral administration were used.Beagle dogs were selected as subjects,and the drug concentration of plasma samples was determined by LC-MS/MS.Through the estimation of pharmacokinetic parameters and statistical analysis,the absorption and elimination process,relative bioavailability and in vivo accumulation effect were evaluated,and pharmacokinetic characteristics of mesalazine enteric sustained-release granules were compared with those marketed preparations.Results After a single dose oral administration(gavage)of mesalazine enteric sustained-release granules in Beagle dogs,the relative bioavailability of mesalazine enteric sustained-release granules was 101.30%±20.20%and 109.20%±30.80%,respectively,compared with that of mesalazine sustained-release granules and mesalazine enteric coated tablets.There was no accumulation effect in vivo after oral administration(gavage)of multiple doses.Mesalazine enteric sustained-release granules had no significant difference from the two preparations sold in the statistical analysis and market through the statistical analysis and comparison of pharmacokinetic parameters and relative bioavailability.Conclusion The absorption and elimination process of mesalazine enteric sustained-release granules shows linear dynamic characteristics.It reaches steady state and has no accumulation in vivo about 5 days after multi-dose administration.There is no significant difference between the pharmacokinetic parameters of mesalazine enteric sustained-release granules and those of commercial preparations.
作者
胡北
马群
许子华
HU Bei;MA Qun;XU Zi-hua(Department of Pharmacy,General Hospital of Northern Theater Command,Shenyang 110016,China)
出处
《实用药物与临床》
CAS
2020年第7期603-608,共6页
Practical Pharmacy and Clinical Remedies
关键词
美沙拉嗪
肠溶缓释颗粒剂
药代动力学
Mesalazine
Enteric sustained-release granules
Pharmacokinetics
