Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese wom...Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： 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 （Kal）, 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. Results： 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. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.展开更多
目的探讨骨碎补总黄酮防治骨质疏松的机理,为补肾中药有效成分治疗骨质疏松症提供实验依据。方法选取3月龄雌性SD大鼠72只,随机分为6组:给药组切除双侧卵巢给予骨碎补总黄酮灌胃,分为:高剂量组,中剂量组,低剂量组;对照组,切除双侧卵巢...目的探讨骨碎补总黄酮防治骨质疏松的机理,为补肾中药有效成分治疗骨质疏松症提供实验依据。方法选取3月龄雌性SD大鼠72只,随机分为6组:给药组切除双侧卵巢给予骨碎补总黄酮灌胃,分为:高剂量组,中剂量组,低剂量组;对照组,切除双侧卵巢给予雌激素灌胃;假手术组,开腹后切除一小块卵巢周围脂肪给予常规喂饲;空白组不做处理常规喂饲。分别在第0、3、6个月处死每次每组4只。取左胫骨近端干骺端标本,运用荧光定量PCR方法测定Cathepsin K mRNA表达量,运用三点弯曲法测胫骨干最大弯曲载荷,采用SPSS软件进行数据统计分析。结果给药组与对照组胫骨干骺端Cathepsin K mRNA表达量相比,有统计学意义(P<0.05)。给药组与假手术,空白组均有显著性差异(P<0.01);胫骨干最大弯曲载荷显示:给药组与对照组有统计学意义(P<0.05),给药组与假手术,空白组均有显著性差异(P<0.01)。结论骨碎补总黄酮可以降低胫骨干骺端Cathepsin KmRNA的表达量,提高胫骨干最大弯曲载荷。此可能为骨碎补总黄酮治疗骨质疏松症的重要机制。展开更多
基金Supported by Significant Drug Research and Development in Important State Science and Technology Specific and Key Technique Research(No.2009ZX09502-030)
文摘Objective： To evaluate the effect of covariates on the pharmacokinetic profiles of naringin in the total flavonoids of Drynaria fortunei （Kunze） J. Sin. in the Qianggu Capsule （强骨胶囊） by evaluating Chinese women with primary osteoporosis. Methods： 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 （Kal）, 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. Results： 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. Conclusion： The pharmacokinetic behaviors of naringin are altered with hyperlipidemia in Chinese women with primary osteoporosis.
文摘目的探讨骨碎补总黄酮防治骨质疏松的机理,为补肾中药有效成分治疗骨质疏松症提供实验依据。方法选取3月龄雌性SD大鼠72只,随机分为6组:给药组切除双侧卵巢给予骨碎补总黄酮灌胃,分为:高剂量组,中剂量组,低剂量组;对照组,切除双侧卵巢给予雌激素灌胃;假手术组,开腹后切除一小块卵巢周围脂肪给予常规喂饲;空白组不做处理常规喂饲。分别在第0、3、6个月处死每次每组4只。取左胫骨近端干骺端标本,运用荧光定量PCR方法测定Cathepsin K mRNA表达量,运用三点弯曲法测胫骨干最大弯曲载荷,采用SPSS软件进行数据统计分析。结果给药组与对照组胫骨干骺端Cathepsin K mRNA表达量相比,有统计学意义(P<0.05)。给药组与假手术,空白组均有显著性差异(P<0.01);胫骨干最大弯曲载荷显示:给药组与对照组有统计学意义(P<0.05),给药组与假手术,空白组均有显著性差异(P<0.01)。结论骨碎补总黄酮可以降低胫骨干骺端Cathepsin KmRNA的表达量,提高胫骨干最大弯曲载荷。此可能为骨碎补总黄酮治疗骨质疏松症的重要机制。
