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Application of a Volumetric Absorptive Microsampling Device to a Pharmacokinetic Study of Tacrolimus in Rats: Comparison with Wet Blood and Plasma

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Abstract

Background and Objectives

Volumetric absorptive microsampling (VAMS) devices are useful for sampling a smaller volume of blood from rodents in the preclinical setting. In the present study, we evaluated the proof of concept of a VAMS device by comparing the pharmacokinetic data of tacrolimus in rats among dried blood in VAMS, wet blood, and plasma.

Methods

Tacrolimus was administered orally, to rats, at a dose of 10 mg/kg. Only 10 μL aliquots of blood were absorbed by VAMS devices at designated time points. Tacrolimus was extracted with a methanol–water mixture (1:1, v/v) via sonication. Tacrolimus levels in wet blood (10 μL) and plasma (10 μL) were quantified after protein precipitation.

Results

Tacrolimus in VAMS devices was quantifiable from 0.2 ng/mL using high-performance liquid chromatography with tandem mass spectrometer. Accuracy and precision were within the acceptance criteria. Bland–Altman plots showed that tacrolimus concentrations in VAMS devices were similar to those in wet blood, regardless of tacrolimus levels. On the other hand, tacrolimus levels in plasma were different from those in VAMS devices, especially at lower concentrations, likely due to partition of tacrolimus to blood cells. However, pharmacokinetic parameters were comparable among the three matrices.

Conclusions

Collectively, these findings suggest that the VAMS device can be a useful device for pharmacokinetic studies in rats.

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Acknowledgements

This study was funded by Eisai Co., Ltd. The authors acknowledge Kathleen Vanderhoof for providing editorial assistance.

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Authors and Affiliations

  1. Bioanalysis Unit, Tsukuba R&D Supporting Division, Sunplanet Co., Ltd., Tokodai 5-1-3, Tsukuba-shi, Ibaraki, 300-2635, Japan

    Kenji Kita

  2. Preclinical Safety Research Unit, Tsukuba R&D Supporting Division, Sunplanet Co., Ltd., Tokodai 5-1-3, Tsukuba-shi, Ibaraki, 300-2635, Japan

    Kenichi Noritake

  3. Drug Metabolism and Pharmacokinetics, Eisai Co., Ltd, Tokodai 5-1-3, Tsukuba-shi, Ibaraki, 300-2635, Japan

    Yuji Mano

Authors
  1. Kenji Kita
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Corresponding author

Correspondence to Yuji Mano.

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Funding

This work was sponsored by Eisai Co., Ltd.

Conflict of Interest

Kenji Kita and Kenichi Noritake are employees of Sunplanet Co., Ltd., a subsidiary of Eisai Co. Ltd., and Yuji Mano is an employee of Eisai Co., Ltd.

Ethics Approval

Animal care and experimental procedures were performed in the animal facility accredited by the Health Science Center for Accreditation of Laboratory Animal Care and Use of the Japan Health Sciences Foundation. All protocols were approved by the Institutional Animal Care and Use Committee and carried out in accordance with the Animal Experimentation Regulations of Eisai Co., Ltd.

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Kita, K., Noritake, K. & Mano, Y. Application of a Volumetric Absorptive Microsampling Device to a Pharmacokinetic Study of Tacrolimus in Rats: Comparison with Wet Blood and Plasma. Eur J Drug Metab Pharmacokinet 44, 91–102 (2019). https://doi.org/10.1007/s13318-018-0493-7

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  • DOI: https://doi.org/10.1007/s13318-018-0493-7

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