Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100093, China.
Chin J Integr Med. 2012 Dec;18(12):925-33. doi: 10.1007/s11655-012-1296-0. Epub 2012 Dec 13.
To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei (Kunze) J. Sm. in the Qianggu Capsule () by evaluating Chinese women with primary osteoporosis.
A total of 98 female patients from the communities of Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen in Beijing, China, aged 40 to 80 years, were included in this study. Blood samples were collected before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after a single oral dose of Qianggu Capsule. The concentration in blood samples from 32 patients before and 0.5, 1, 2, 3, and 4 h after drug administration were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and full set of pharmacokinetic data was analyzed with nonlinear mixed-effect modeling (NONMEM) software. The mean of population parameters clearance (C1), central distribution volume (V), absorption rate constant (Ka1), inter-compartmental clearance (C2), peripheral distribution volume (V2) were set as parameters and estimated through base model, covariate model, and final model. Age, height, weight, blood urea nitrogen (BUN), serum creatinine (Scr), alanine transaminase (ALT), aspartate transaminase (AST), hyperlipidemia, Liver (Gan) Kidney (Shen) yin insufficiency (GSYI), Kidney (Shen) yang insufficiency (SYI) were set as covariates.
The relationships between these parameters and covariates were analyzed. The results showed that C1 was the main parameter influenced by the selected covariates among the population parameters, and the relationships between the covariates and C1 were analyzed, among the selected covariates hyperlipidemia was identified as significant covariate of C1.
The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.
通过评估中国原发性骨质疏松症女性患者的药代动力学参数，评价混杂因素对筋骨草总黄酮中柚皮苷在强骨胶囊（）中的药代动力学特征的影响。
本研究共纳入中国北京景山、北新桥、交道口、朝阳门和东四社区年龄在 40 岁至 80 岁之间的 98 名女性患者。这些患者单次口服强骨胶囊后，在 0.5、1、2、3、4、6、8、10、12 和 24 h 分别采集血样。采用液相色谱-串联质谱（LC-MS/MS）法测定 32 例患者给药前和给药后 0.5、1、2、3 和 4 h 的血样浓度，采用非线性混合效应模型（NONMEM）软件分析全数据集的药代动力学参数。采用基础模型、协变量模型和最终模型，将群体参数清除率（C1）、中央分布容积（V）、吸收速率常数（Ka1）、隔室间清除率（C2）、外周分布容积（V2）的平均值作为参数进行估计。年龄、身高、体重、血尿素氮（BUN）、血清肌酐（Scr）、丙氨酸转氨酶（ALT）、天门冬氨酸转氨酶（AST）、高脂血症、肝（Gan）肾（Shen）阴虚（GSYI）、肾（Shen）阳虚（SYI）被设定为协变量。
分析了这些参数与协变量之间的关系。结果表明，在群体参数中，C1 是受所选协变量影响的主要参数，分析了协变量与 C1 之间的关系，其中高脂血症被确定为 C1 的显著协变量。
在患有原发性骨质疏松症的中国女性中，柚皮苷的药代动力学行为会因高脂血症而发生改变。
