title: Effect of naringenin in Qianggu capsule on population pharmacokinetics in Chinese women with primary osteoporosis.
abstract: 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 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, C1, 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Wang
authors.initials: W
authors.lastname: Jiannong
authors.forename: Jiang
authors.initials: J
authors.lastname: Junjie
authors.forename: Xie
authors.initials: X
authors.lastname: Yanming
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Jianpeng
authors.forename: Duan
authors.initials: D
authors.lastname: Jingli
authors.forename: Xiong
authors.initials: X
authors.lastname: Xin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002214:Capsules / Q000008:administration & dosage; D002681:China; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D010024:Osteoporosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D002214:Capsules; D004365:Drugs, Chinese Herbal; D044950:Flavanones; C005273:naringenin