• Minako Ishii-Maruhama, Hitoshi Higuchi, Mai Nakanou, Yuka Honda-Wakasugi, Akiko Yabuki-Kawase, Shigeru Maeda, and Takuya Miyawaki.
• 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.
• J Anesth. 2018 Oct 1; 32 (5): 688-693.

PurposeIt 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.MethodsSerum 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).ResultsIn 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.ConclusionVPA might increase the proportion of protein-unbound-free propofol in human serum via displacement reactions.

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