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Strategies for developing Alzheimer’s disease treatments: application of population pharmacokinetic and pharmacodynamic models

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Abstract

Background

As the number of Alzheimer's disease (AD) patients steadily increases, many pharmaceutical industries and researchers are making efforts and investments in developing AD treatments. However, numerous AD new drug candidates are frustrated with clearing the hurdles in clinical trials, and few AD treatments have been approved by regulatory agencies worldwide. In order to develop AD treatments, it is essential to consider the characteristics of AD itself and AD patients, and to devise evaluation methods deriving significant clinical safety and efficacy.

Area covered

This review focused on pharmacometrics, the latest mechanism-based PK/PD modeling and simulation approaches among strategies for developing AD treatments. Including the basic concept of pharmacometrics, several cases of applying pharmacometrics to AD treatments in the approval or development stage were categorized as PK, PD, and PK-PD models and reviewed.

Expert opinion

Unlike traditional PK/PD models, the population model-based PK/PD evaluations could apply to sparse data collected from a heterogeneous population. Various covariate factors in patients receiving AD treatments were investigated and quantified through the developed and validated population models. Investigating potential covariates of AD treatments could be employed to optimize the dosage regimen for AD patients. Consequently, a summary of the population PK/PD model will be useful information for clinical pharmacometricians and contribute to the development of AD treatments in the future in decision-making such as dosage optimization.

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Acknowledgements

This research was supported by the Korea Health Industry Development Institute (KHIDI) grant, funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HF20C0016).

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Author notes

  1. Dong Wook Kang and Seok-jin Cho have contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea

    Dong Wook Kang, Seok-jin Cho & Hea-Young Cho

  2. Pharmaceutical Research Center, Hanmi Pharmaceutical Co., Ltd., Suwon-si, Gyeonggi-do, 16229, Republic of Korea

    Go-Wun Choi

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  1. Dong Wook Kang
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Correspondence to Hea-Young Cho.

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All authors (D.W. Kang, S.-j. Cho, G.-W. Choi, H.-Y. Cho) declare that they have no conflict of interest.

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Kang, D.W., Cho, Sj., Choi, GW. et al. Strategies for developing Alzheimer’s disease treatments: application of population pharmacokinetic and pharmacodynamic models. J. Pharm. Investig. 52, 519–538 (2022). https://doi.org/10.1007/s40005-022-00579-7

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