Population Pharmacokinetics of Naoqingzhiming Tablets a Novel Drug for Vascular Dementia in Healthy Chinese Subjects

Population Pharmacokinetics of Naoqingzhiming Tablets a Novel Drug for Vascular Dementia in Healthy Chinese Subjects

Loading document ...
Page
of
Loading page ...

Author(s)

Author(s): Xin Liu, Pingping Lin, Ting Li, Ping Shi, Chenjing Wang, Lujin Li, Yu Cao

Download Full PDF Read Complete Article

DOI: 10.18483/ijSci.2594 13 24 5-11 Volume 11 - Jun 2022

Abstract

Objective The aims of this study was to develop a population pharmacokinetic model to characterize the pharmacokinetics of Naoqingzhiming tablets (ingredient: echinacoside) following single and multiple doses in healthy Chinese subjects, and to identify covariates that might explain variability in exposure following oral administration. Methods Model development was achieved using data from a single- and multiple-dose studies. 1497 blood concentrations were available for population pharmacokinetics model. Population pharmacokinetic modelling was conducted using nonlinear mixed-effects modelling (NONMEM) software to estimate population pharmacokinetic parameters. Results A two-compartment model with first order absorption and elimination was found to best describe the pharmacokinetics of Naoqingzhiming tablets. The final model included aspartate aminotransferase (AST) as a covariate on apparent volume of distribution (V/F). The final pharmacokinetic parameter estimates were apparent clearance, 2510L/h; apparent volume of distribution, 11200L; and lag time, 0.141h. Conclusion The population pharmacokinetic model for Naoqingzhiming tablets identified the relationship between pharmacokinetic parameters and covariates, apparent volume of distribution was related to aspartate aminotransferase.

Keywords

Echinacoside, Population Pharmacokinetics, Modeling, Naoqingzhiming Tablets

References

  1. Llibre Rodriguez, J. J., Ferri, C. P., & Acosta, D., et al. (2008). Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey. Lancet (London, England), 372(9637), 464–474. https://doi.org/10.1016/S0140-6736(08)61002-8
  2. Wimo, A., Winblad, B., & Jönsson, L. (2010). The worldwide societal costs of dementia: Estimates for 2009. Alzheimer's & dementia: the journal of the Alzheimer's Association, 6(2), 98–103. https://doi.org/10.1016/j.jalz.2010.01.010
  3. Wolters, F. J., & Ikram, M. A. (2019). Epidemiology of Vascular Dementia. Arteriosclerosis, thrombosis, and vascular biology, 39(8), 1542–1549. https://doi.org/10.1161/ATVBAHA.119.311908
  4. Korczyn A. D. (2002). The complex nosological concept of vascular dementia. Journal of the neurological sciences, 203-204, 3–6. https://doi.org/10.1016/s0022-510x(02)00251-4
  5. Sinha, K., Sun, C., Kamari, R., et al. (2020). Current status and future prospects of pathophysiology-based neuroprotective drugs for the treatment of vascular dementia. Drug discovery today, 25(4), 793–799. https://doi.org/10.1016/j.drudis.2020.01.003
  6. Farooq, M. U., Min, J., Goshgarian, C., et al. (2017). Pharmacotherapy for Vascular Cognitive Impairment. CNS drugs, 31(9), 759–776. https://doi.org/10.1007/s40263-017-0459-3
  7. Song, Y., Zeng, K., Jiang, Y., et al. (2021). Cistanches Herba, from an endangered species to a big brand of Chinese medicine. Medicinal research reviews, 41(3), 1539–1577. https://doi.org/10.1002/med.21768
  8. Deng, M., Zhao, J. Y., Tu, P. F., et al. (2004). Echinacoside rescues the SHSY5Y neuronal cells from TNFalpha-induced apoptosis. European journal of pharmacology, 505(1-3), 11–18. https://doi.org/10.1016/j.ejphar.2004.09.059
  9. Feng, X. Y., Zhu, M., Zhang, Q. Q., et al. (2012). Selective protection of nigral dopaminergic neurons by echinacoside in a rat model of Parkinson disease induced by rotenone. Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine, 10(7), 777–783. https://doi.org/10.3736/jcim20120708
  10. Wei, L. L., Chen, H., Jiang, Y., et al. (2012). Effects of echinacoside on histio-central levels of active mass in middle cerebral artery occlusion rats. Biomedical and environmental sciences: BES, 25(2), 238–244. https://doi.org/10.3967/0895-3988.2012.02.017
  11. Brendel, K., Dartois, C., Comets, E., et al. (2007). Are population pharmacokinetic and/or pharmacodynamic models adequately evaluated? A survey of the literature from 2002 to 2004. Clinical pharmacokinetics, 46(3), 221–234. https://doi.org/10.2165/00003088-200746030-00003
  12. Plassman, B. L., Langa, K. M., Fisher, G. G., et al. (2007). Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology, 29(1-2), 125–132. https://doi.org/10.1159/000109998
  13. Chan, K. Y., Wang, W., Wu, J. J., et al. Global Health Epidemiology Reference Group (GHERG) (2013). Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010: a systematic review and analysis. Lancet (London, England), 381(9882), 2016–2023. https://doi.org/10.1016/S0140-6736(13)60221-4
  14. Kalaria, R. N., Maestre, G. E., Arizaga, R., et al. (2008). Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors. The Lancet. Neurology, 7(9), 812–826. https://doi.org/10.1016/S1474-4422(08)70169-8
  15. Korczyn, A. D., Vakhapova, V., & Grinberg, L. T. (2012). Vascular dementia. Journal of the neurological sciences, 322(1-2), 2–10. https://doi.org/10.1016/j.jns.2012.03.027
  16. Liu, J., Yang, L., Dong, Y., et al. (2018). Echinacoside, an Inestimable Natural Product in Treatment of Neurological and other Disorders. Molecules (Basel, Switzerland), 23(5), 1213. https://doi.org/10.3390/molecules23051213
  17. Fu, Z., Fan, X., Wang, X., et al. (2018). Cistanches Herba: An overview of its chemistry, pharmacology, and pharmacokinetics property. Journal of ethnopharmacology, 219, 233–247. https://doi.org/10.1016/j.jep.2017.10.015
  18. Jia, C., Shi, H., Jin, W., et al. (2009). Metabolism of echinacoside, a good antioxidant, in rats: isolation and identification of its biliary metabolites. Drug metabolism and disposition: the biological fate of chemicals, 37(2), 431–438. https://doi.org/10.1124/dmd.108.023697
  19. Kalaria R. N. (2018). The pathology and pathophysiology of vascular dementia. Neuropharmacology, 134(Pt B), 226–239. https://doi.org/10.1016/j.neuropharm.2017.12.030
  20. Wen, Y., Huo, S., Zhang, W., , et al. (2016). Pharmacokinetics, Biodistribution, Excretion and Plasma Protein Binding Studies of Acteoside in Rats. Drug research, 66(3), 148–153. https://doi.org/10.1055/s-0035-1555896

Cite this Article:

International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.

Search Articles

Issue July 2022

Volume 11, July 2022


Table of Contents



World-wide Delivery is FREE

Share this Issue with Friends:


Submit your Paper