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

OBJECTIVE: To characterize naringenin (NAR) population 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, received 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 (Cl), 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 step-wise 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 first order degradation was the best fitted to the concentration-time profiles following oral administration of NAR. The mean of population parameters of the final model, Cl, SYAX on C1, V, Ka1, CLII, and VII, Were measured to be 37.6 L/h, 0.427 L, 123 L/h, 0.12/h, 0.3056, and 1.446, respectively. Inter-individual variability was estimated and SYAX was identified as a significant covariate. CONCLUSION: The population pharmacokinetic model described in this study could effectively characterize the pharmacokinetic profile of NAR following administration of a single dose of oral Qianggu capsules in Chinese women with primary osteoporosis. Among the tested covariates, only SYAX was a significant factor. (C) 2015 JTCM. All rights reserved.Supported by Grant from Significant Drug Research and Development in Important State Science and Technology Specific And Key Technique Research (Key Issues Research on Re-evaluation of Listed Herbal Hedicine),Visiting Fellow Joint Innovation Research Project of The China Academy of Chinese Medical Sciences (Exploratory Research in Population Pharmacokinetics of Bioactive Compounds of Osteopractic Total Flavone Based on Total Quantum Statistical...)SCI(E)中国科学引文数据库(CSCD)ARTICLEDatamining5288@163.com2141-1533