TY - JOUR
T1 - In vitro changes in the proportion of protein-unbound-free propofol induced by valproate
AU - Maruhama, Minako
AU - Higuchi, Hitoshi
AU - Nakanou, Mai
AU - Honda-Wakasugi, Yuka
AU - Kawase, Akiko
AU - Maeda, Shigeru
AU - Miyawaki, Takuya
N1 - Funding Information:
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.
Publisher Copyright:
© 2018, Japanese Society of Anesthesiologists.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
KW - Antiepileptic drugs
KW - Drug interactions
KW - Propofol
KW - Serum protein
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U2 - 10.1007/s00540-018-2540-6
DO - 10.1007/s00540-018-2540-6
M3 - Article
C2 - 30062394
AN - SCOPUS:85051085867
VL - 32
SP - 688
EP - 693
JO - Journal of Anesthesia
JF - Journal of Anesthesia
SN - 0913-8668
IS - 5
ER -