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Pharmacokinetics of Rasagiline in Healthy Adult Chinese Volunteers with Various Genotypes: A Single-Center, Open-Label, Multiple-Dose Study

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Abstract

Background and Objective

Although there is evidence indicating cytochome P450 (CYP) 1A2 is responsible for the metabolism of rasagiline, the role of other CYP isoforms is unclear. This study investigated the pharmacokinetics of rasagiline in adult Chinese healthy volunteers with various CYP genotypes.

Methods

This single-center, open-label study was conducted in 12 subjects. Fasted subjects received rasagiline 1 mg daily for 7 days. Blood samples were taken to determine plasma concentrations of rasagiline, its major metabolite R-1-aminoindan (AI), and the genotyping of CYP2D6 and CYP2C19. Safety was also assessed.

Results

After oral administration, rasagiline was absorbed with a median time to reach maximum concentration (t max) of 0.5 h. Overall systemic exposure was approximately theefold on day 7 versus day 1. The mean terminal elimination half-life (t ½) was nearly doubled on day 7 compared to day 1. AI was rapidly quantifiable in plasma with median t max occurring 1–1.5 h post-dose. Overall exposure to AI on day 7 was approximately twofold higher than on day 1. Overall systemic exposure to AI was approximately four- to sixfold greater than exposure to rasagiline, whereas maximum concentration (C max) was approximately half that of rasagiline. The mean t ½ for AI was longer than for the parent drug, and was similar between the sexes and days. Inferred metabolic status did not appear to affect the pharmacokinetics of rasagiline or AI. All adverse events were mild to moderate in severity.

Conclusion

Multiple oral administration of rasagiline 1 mg tablet in Chinese healthy adults resulted in similar pharmacokinetics of both rasagiline and AI compared to those previously observed in Caucasians. Rasagiline was safe and well tolerated in Chinese healthy volunteers.

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Author notes

    Authors and Affiliations

    1. Phase I Unit, Clinical Pharmacological Research Centre, Peking Union Medical College Hospital, 41# Damucang Hutong, Xicheng District, Beijing, 10032, China

      Xia Chen, Qian Zhao, Ji Jiang, Jian Liu & Pei Hu

    Authors
    1. Xia Chen
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    2. Qian Zhao
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    3. Ji Jiang
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    4. Jian Liu
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    5. Pei Hu
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    Corresponding author

    Correspondence to Pei Hu.

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    Funding

    The study was funded by H. Lundbeck A/S, Denmark.

    Conflict of interest

    Xia Chen, Qian Zhao, Ji Jiang, Jian Liu, and Pei Hu have no conflicts of interest.

    Ethical approval

    The study was conducted in accordance with International Conference on Harmonization Good Clinical Practice guidelines, all applicable subject privacy requirements, and the ethical principles outlined in the Declaration of Helsinki. The study design was approved by the ethics committee of PUMCH.

    Informed consent

    Informed consent was obtained for participating in the study and for taking blood samples for genotyping assessments from all individual participants included in the study.

    Additional information

    Xia Chen and Qian Zhao are equal first authors for this manuscript contributed.

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    Cite this article

    Chen, X., Zhao, Q., Jiang, J. et al. Pharmacokinetics of Rasagiline in Healthy Adult Chinese Volunteers with Various Genotypes: A Single-Center, Open-Label, Multiple-Dose Study. Clin Drug Investig 36, 369–376 (2016). https://doi.org/10.1007/s40261-016-0380-4

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    • DOI: https://doi.org/10.1007/s40261-016-0380-4

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