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Influence of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine in adult patients receiving CHOP therapy

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Abstract

Purpose

This study aims to clarify the impact of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine (VCR) in adult patients receiving CHOP therapy.

Methods

Plasma samples were collected immediately after the end of VCR administration and at 1.5, 2.5, 3.5, 5.5, 9.5, 13.5, and 25.5 h after the start of administration. Areas under the plasma concentration–time curves of VCR in the elimination phase (AUC1.5–25.5) were calculated using the linear trapezoidal rule. Half-lives of VCR during the early phase (1.5–5.5 h) and terminal phase (5.5–25.5 h; t1/2γ) were determined according to the log-linear regression of the concentration–time data for at least 3 sampling points.

Results

A total of 41 adult patients were enrolled in this study. The median t1/2γ and AUC1.5–25.5 were significantly longer and higher in CYP3A5 non-expressers (CYP3A5*3/*3) than in CYP3A5 expressers (CYP3A5*1/*1 or *1/*3) (21.3 vs 13.8 h, P = 0.005 and 35.5 vs 30.0 ng･h/mL, P = 0.006, respectively). Conversely, there were no significant differences in pharmacokinetic parameters among the ABCB1 c.1236C>T, c.2677G>A/T, c.3435C>T genotype groups. A stepwise selection multiple linear regression analysis showed that the dose of VCR administered and CYP3A5 non-expresser status were independent factors influencing the AUC1.5–25.5 (partial R2 = 0.212, P = 0.002 and partial R2 = 0.143, P = 0.010, respectively).

Conclusion

The CYP3A5*3 polymorphism was found to be an indicator for predicting exposure to VCR in adult patients receiving CHOP therapy. This information may be useful for the individualization of VCR dosages.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Funding

The authors did not receive support from any organization for this manuscript.

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Authors and Affiliations

  1. Department of Pharmacy, Hirosaki University Hospital, 53 Hon-cho, Hirosaki, Aomori, 036-8563, Japan

    Junichi Nakagawa, Keigo Saito, Kayo Ueno & Takenori Niioka

  2. Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, Japan

    Takenori Takahata, Kosuke Kamata, Takuto Tachita, Satoru Yamashita & Hirotake Sakuraba

  3. Department of Medical Oncology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, Japan

    Yu Chen, Kensuke Saito & Atsushi Sato

  4. Department of Pharmaceutical Science, Hirosaki University Graduate School of Medicine, 53 Hon-cho, Hirosaki, Aomori, Japan

    Takenori Niioka

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  1. Junichi Nakagawa
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Contributions

Conceptualization, TN; investigation, TT, YC, KS, KK, TT, SY, and KS; measurement of anticancer drugs, J.N. and K.U.; formal analysis, JN; writing—original draft preparation, JN; writing—review and editing, AS, HS, and TN. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Takenori Niioka.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Hirosaki University Graduate School of Medicine (project identification code: 2018-055) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in this study.

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Nakagawa, J., Takahata, T., Chen, Y. et al. Influence of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine in adult patients receiving CHOP therapy. Cancer Chemother Pharmacol 92, 391–398 (2023). https://doi.org/10.1007/s00280-023-04580-1

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