多元多水平模型对多奈哌齐口腔崩解片与普通片生物等效性的研究

发布时间：2018-07-17 00:53

【摘要】：目的采用多元多水平模型评价多奈哌齐口腔崩解片与普通片的生物等效性。方法 22例受试志愿者单次交叉口服多奈哌齐口腔崩解片(试验药)5 mg和多奈哌齐普通片(参比药)5 mg,采用高效液相色谱-串联质谱法测定给药后各时间点经时血药浓度,通过逐步建立模型来分析生物等效性。首先建立零模,探究ρ_(max)和AUC_(0-t)在阶段水平和个体水平的聚集性,从而进一步建立单元多水平模型。由于ρ_(max)和AUC_(0-t)两指标间存在相关性,因此最终建立多元多水平模型进行生物等效性的评价。结果模型显示多水平结构随机效应有显著差异(P0.05),且ρ_(max)和AUC_(0-t)两指标在多水平中具有强相关性。试剂固定效应参数不存在显著差异,两指标90%联合置信区间在(-0.020,-0.007)之间。结论多元多水平模型用于生物等效性分析可有效解释变异,缩小置信区间范围。多奈哌齐口腔崩解片和多奈哌齐普通片生物等效。
[Abstract]:Objective to evaluate the bioequivalence of Donepezil oral disintegrating tablets and common tablets by multivariate multilevel model. Methods 22 volunteers were randomly divided into two groups: oral disintegrating tablets (5 mg) and conventional tablets (reference drug) 5 mg. Blood concentrations were determined by high performance liquid chromatography-tandem mass spectrometry (HPLC / MS). The bioequivalence is analyzed by building a model step by step. At first, zero modules are established to explore the aggregation of 蟻 _ (max) and AUC0-t at stage level and individual level, so as to further establish the multi-level model of unit. Because of the correlation between 蟻 _ (max) and AUC0-t, a multivariate multilevel model was established to evaluate the bioequivalence. Results the random effects of multi-level structures were significantly different (P0.05), and 蟻 _ (max) and AUC0-t had strong correlation in multiple levels. There was no significant difference in the fixed effect parameters of the reagent, and the 90% combined confidence interval of the two indexes was between (-0.020 ~ 0.007). Conclusion the multivariate multilevel model used in bioequivalence analysis can effectively explain the variation and reduce the confidence interval. Donepezil oral disintegrating tablets and Donepezil tablets were bioequivalent.
【作者单位】：四川大学华西公共卫生学院流行病与统计学系;四川大学华西医院国家药物临床试验机构;
【分类号】：R969

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