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In vitro changes in the proportion of protein-unbound-free propofol induced by valproate

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Abstract

Purpose

It has been reported that oral valproate (VPA) reduces the dose of propofol required for sedation. As  a potential reason for this, it is considered that VPA displaces serum protein-bound propofol and increases the proportion of protein-unbound-free propofol. To examine this hypothesis, the present in vitro study investigated the influence of VPA on the proportion of protein-unbound-free propofol in human serum samples.

Methods

Serum samples were collected from 10 healthy volunteers, who were not taking any medication. VPA (final concentration: 0.05, 0.1 or 1 mg/mL) and propofol (final concentration: 1 or 5 µg/mL) were mixed with serum samples with normal (4.0 g/dL) or low (2.5 g/dL) albumin concentrations. Then, protein-unbound-free propofol was extracted from the samples, and its concentration was measured using high-performance liquid chromatography. We compared the proportion of protein-unbound-free propofol in each of the VPA-containing samples with that in serum samples without VPA (control).

Results

In the serum samples with normal albumin concentrations, 1 mg/mL VPA significantly increased the proportion of protein-unbound-free propofol at 1 and 5 µg/mL propofol. Furthermore, in the serum samples with low albumin concentrations, the proportion of protein-unbound-free propofol was significantly increased by both 0.1 and 1 mg/mL VPA at propofol concentrations of 1 and 5 µg/mL.

Conclusion

VPA might increase the proportion of protein-unbound-free propofol in human serum via displacement reactions.

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Funding

The present study was supported by institutional funding of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and a Grant-in-Aid for Young Scientists (B) (24792214) from the Japan Society for Promotion of Science.

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Author notes

  1. Minako Ishii-Maruhama

    Present address: Department of Anesthesiology and ICM, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan

  2. Minako Ishii-Maruhama and Hitoshi Higuchi have contributed equally to this work.

Authors and Affiliations

  1. Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Minako Ishii-Maruhama, Mai Nakanou, Yuka Honda-Wakasugi & Takuya Miyawaki

  2. Department of Dental Anesthesiology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Hitoshi Higuchi, Akiko Yabuki-Kawase & Shigeru Maeda

Authors
  1. Minako Ishii-Maruhama
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  2. Hitoshi Higuchi
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  3. Mai Nakanou
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  4. Yuka Honda-Wakasugi
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  5. Akiko Yabuki-Kawase
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  6. Shigeru Maeda
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  7. Takuya Miyawaki
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Corresponding author

Correspondence to Hitoshi Higuchi.

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Ishii-Maruhama, M., Higuchi, H., Nakanou, M. et al. In vitro changes in the proportion of protein-unbound-free propofol induced by valproate. J Anesth 32, 688–693 (2018). https://doi.org/10.1007/s00540-018-2540-6

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  • DOI: https://doi.org/10.1007/s00540-018-2540-6

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