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 language | English |
|---|---|
| Journal | Journal of Anesthesia |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2018 |
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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 journal › Article
}
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
C2 - 30062394
AN - SCOPUS:85051085867
JO - Journal of Anesthesia
JF - Journal of Anesthesia
SN - 0913-8668
ER -