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Pharmacokinetics of voriconazole and its alteration by Candida albicans infection in silkworms

The Journal of Antibiotics volume 74, pages 443–449 (2021)Cite this article

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Abstract

Voriconazole (VRCZ) is a triazole antifungal agent used for the treatment and prophylaxis of invasive fungal infections. Therapeutic drug monitoring of VRCZ is widely applied clinically because of the large inter-individual variability that is generally observed in VRCZ exposure. The blood levels of VRCZ are increased during an underlying inflammatory reaction, which is associated with infections. Silkworms are useful experimental animals for evaluating the pharmacokinetics and toxicity of compounds. In this study, we investigated the pharmacokinetic parameters, such as elimination half-life, clearance, and distribution volume of VRCZ using silkworms. The pharmacokinetic parameters of VRCZ were determined based on the concentrations in silkworm hemolymph after injection of VRCZ. The elimination half-life of VRCZ in silkworms was found to be similar to that observed in humans. In addition, we assessed the impact of Candida albicans infection on VRCZ concentrations in a silkworm infection model. The VRCZ concentration at 12 h after injection in the Candida albicans-infected group was significantly higher than that in the non-infected group. In the silkworm infection model, we were able to reproduce the relationship between inflammation and VRCZ blood concentrations, as observed in humans. We demonstrate that silkworms can be an effective alternative model animal for studying the pharmacokinetics of VRCZ. We also show that silkworms can be used to indicate essential infection and inflammation-based pharmacokinetic variations in VRCZ, which is usually observed in the clinic.

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Acknowledgements

We thank Tae Nagamachi and Asami Yoshikawa (Meiji Pharmaceutical University) for their technical assistance in rearing the silkworms. This project was supported by JSPS KAKENHI grant number JP20K16095 (Early-Career Scientists to TY) and JP20K07022 (Scientific Research (C) to YM).

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Authors and Affiliations

  1. Department of Medicinal Therapy Research, Pharmaceutical Education and Research Center, Meiji Pharmaceutical University, Kiyose, Japan

    Takeo Yasu

  2. Department of Microbiology, Meiji Pharmaceutical University, Kiyose, Japan

    Yasuhiko Matsumoto & Takashi Sugita

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  1. Takeo Yasu
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Correspondence to Takeo Yasu or Yasuhiko Matsumoto.

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Yasu, T., Matsumoto, Y. & Sugita, T. Pharmacokinetics of voriconazole and its alteration by Candida albicans infection in silkworms. J Antibiot 74, 443–449 (2021). https://doi.org/10.1038/s41429-021-00428-z

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