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

Minako Ishii-Maruhama, Hitoshi Higuchi, Mai Nakanou, Yuka Honda-Wakasugi, Akiko Kawase, Shigeru Maeda, Takuya Miyawaki

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of Anesthesia
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Valproic Acid
Propofol
Proteins
Serum
Albumins
In Vitro Techniques
Blood Proteins
Healthy Volunteers
High Pressure Liquid Chromatography

Keywords

  • Antiepileptic drugs
  • Drug interactions
  • Propofol
  • Serum protein

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

In vitro changes in the proportion of protein-unbound-free propofol induced by valproate. / Ishii-Maruhama, Minako; Higuchi, Hitoshi; Nakanou, Mai; Honda-Wakasugi, Yuka; Kawase, Akiko; Maeda, Shigeru; Miyawaki, Takuya.

In: Journal of Anesthesia, 01.01.2018.

Research output: Contribution to journalArticle

@article{63c45dc5ac714e65a2b4188bcaf24494,
title = "In vitro changes in the proportion of protein-unbound-free propofol induced by valproate",
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.",
keywords = "Antiepileptic drugs, Drug interactions, Propofol, Serum protein",
author = "Minako Ishii-Maruhama and Hitoshi Higuchi and Mai Nakanou and Yuka Honda-Wakasugi and Akiko Kawase and Shigeru Maeda and Takuya Miyawaki",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00540-018-2540-6",
language = "English",
journal = "Journal of Anesthesia",
issn = "0913-8668",
publisher = "Springer Japan",

}

TY - JOUR

T1 - In vitro changes in the proportion of protein-unbound-free propofol induced by valproate

AU - Ishii-Maruhama, Minako

AU - Higuchi, Hitoshi

AU - Nakanou, Mai

AU - Honda-Wakasugi, Yuka

AU - Kawase, Akiko

AU - Maeda, Shigeru

AU - Miyawaki, Takuya

PY - 2018/1/1

Y1 - 2018/1/1

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

UR - http://www.scopus.com/inward/record.url?scp=85051085867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051085867&partnerID=8YFLogxK

U2 - 10.1007/s00540-018-2540-6

DO - 10.1007/s00540-018-2540-6

M3 - Article

JO - Journal of Anesthesia

JF - Journal of Anesthesia

SN - 0913-8668

ER -