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Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Purpose

We performed population pharmacokinetic (PK) analysis of a novel transdermal donepezil patch in healthy subjects who participated in a phase I trial. We also studied the optimal dosage regimen with repeated patch application for achieving a therapeutic range using a PK simulation model.

Methods

This study used data from a randomized, single-dose escalation phase I clinical trial conducted in Korea. The population PK analysis was performed using NONMEM software, version 7.3. From the final PK model, we simulated repeat patch application results assuming various transdermal absorption rates.

Results

Based on the clinical trial data, novel donepezil patches with doses of 43.75 mg/12.5 cm2, 87.5 mg/25 cm2, and 175 mg/50 cm2 were placed on each subject. A linear one-compartment, first-order elimination with sequential zero- and first-order absorption model best described the donepezil plasma concentrations after patch application. Simulated results on the basis of the PK model showed that repeat application of the patches of 87.5 mg/25 cm2 and 175 mg/50 cm2 every 72 h would cover the therapeutic range of donepezil and reach steady-state faster with fewer fluctuations in concentration compared to typical oral administrations.

Conclusion

A linear one-compartment with sequential zero- and first-order absorption model was effective for describing the PKs of donepezil after application of patch. Based on this analysis, 87.5 mg/25 cm2 or 175 mg/50 cm2 patch application every 72 h is expected to achieve the desired plasma concentration of donepezil.

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Acknowledgments

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI07C0001).

Conflict of interest

The authors declare no conflicts of interest. The phase I clinical trial which provided the data used in this study was sponsored by Icure, Inc. (Gyeonggi-do, Republic of Korea).

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea

    Hee Youn Choi, Yo Han Kim, Kyun-Seop Bae & Hyeong-Seok Lim

  2. University of Ulsan College of Medicine, Seoul, Korea

    Hee Youn Choi, Yo Han Kim, Kyun-Seop Bae & Hyeong-Seok Lim

  3. iCure Pharmaceutical Incorporated, Anseong, Gyeonggi-do, Korea

    Donghyun Hong & Seong Su Kim

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  1. Hee Youn Choi
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Correspondence to Kyun-Seop Bae.

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Choi, H.Y., Kim, Y.H., Hong, D. et al. Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers. Eur J Clin Pharmacol 71, 967–977 (2015). https://doi.org/10.1007/s00228-015-1875-2

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  • DOI: https://doi.org/10.1007/s00228-015-1875-2

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