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Investigation of pharmacokinetics of cyclosporine with NONMEM in type 1 diabetic rat model
Author(s): 
Pages: 630-633
Year: Issue:  11
Journal: Qilu Pharmaceutical Affairs

Keyword:  糖尿病大鼠环孢素非线性混合效应模型法药代动力学参数;
Abstract: 目的 研究糖尿病对环孢素A(ciclosporin A,CsA)体内药物代谢动力学的影响.方法 大鼠腹腔注射65 mg?kg-1链脲菌素(STZ)建立1型糖尿病大鼠模型.造模5周后通过荧光偏振免疫分析(FPIA)法检测大鼠灌胃环孢素(10 mg?kg-1)后全血中的环孢素浓度,采用非线性混合效应模型法(nonlinear mixed effect model,NON-MEM)建立药物代谢动力学模型,贝叶斯(Bayes)反馈法获取个体参数并比较.结果 链腺苗素注射1周后,大鼠空腹血糖超过11.1 mmol?L-1,确认1型糖尿病大鼠造模成功.造模5周后,糖尿病大鼠的血糖显著增高.给药后,环孢素在大鼠体内呈现一房室模型,群体典型值及个体间差异(between subject variability,BSV)分别为:清除率(CL/F)=0.525 L?h-1,个体间差异=32.1%;表观分布容积(V/F)=5.18 L,个体间差异=35.6%;吸收速率常数(Ka)=1.82,个体间差异=71.1%.正常组与糖尿病组大鼠清除率无显著性差异(P>0.05);表观分布容积无显著性差异(P>0.05);吸收速率常数有显著性差异(P<0.05).结论 1型糖尿病大鼠灌胃环孢素的吸收速率常数显著改变,且存在较大的个体间差异,提示糖尿病状态下会影响环孢素的吸收.
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