Effect of naringenin in Qianggu capsule on population pharmacokinetics in Chinese women with primary osteoporosis

作者：Wang Jian-nong, Junjie Jiang, Xie Yanming, Xu Wei, Jianpeng Li, Duan Jing-li, Xin Xiong · 发表于：中医杂志：英文版 · 年份：2015 · DOI：10.1016/s0254-6272(15)30021-2 · 被引用次数：8 · 研究领域：Bone Metabolism and Diseases、Bone health and osteoporosis research、Sphingolipid Metabolism and Signaling

OBJECTIVE: To characterize naringenin (NAR) pop- ulation pharmacokinetics (PPK) in Chinese women with primary osteoporosis. METHODS: Ninety-eight female patients with primary osteoporosis from the Jingshan, Beixinqiao, Jiaodaokou, Chaoyangmen, and Donghuamen communities in Beijing, China, aged 40 to 80 years, re- ceived oral Qianggu capsules (250 mg). Blood samples were collected before and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after administration. The concentration of NAR in the blood samples was measured using high performance liquid chromatography-tandem mass spectrometry. PPK analyses were performed with nonlinear mixed-effect modeling software (version 7.1.2, PsN3.2.12). The clearance (C1), central distribution volume (V), absorption rate constant (Ka1), peripheral distribution volume (VII), and inter-compartmental clearance (CLII) were set as parameters and estimated by the base model, covariate model, and final model. Kidney-Yang deficiency [Shenyangxu (SYAX)] and liver-kidney-Yin deficiency (Ganshenyinxu) are patterns of symptoms in Traditional Chinese Medicine that were set as covariates, along with age, height, blood urea nitrogen, serum creatinine, alanine transaminase, aspartate transaminase, and hyperlipidemia. Both stepwise forward and backward procedures were accomplished to build models. The final model was evaluated by internal and external validation, visual predictive check, bootstrap, and leverage analysis. RESULTS: A one compartment open model with ...