Abstract
Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. We evaluated whether clinical VPA therapy affected the propofol blood level, the protein-unbound free propofol level, and/or the anesthetic effects of propofol in the clinical setting. The subjects were divided into the control group (not medicated with antiepileptics), the mono-VPA group (medicated with VPA alone), and the poly-VPA group (medicated with VPA, other antiepileptics, and/or psychoactive drugs). General anesthesia was induced via the administration of a single bolus of propofol and a remifentanil infusion, and when the bispectral index (BIS) exceeded 60 sevoflurane was started. There were no significant differences in the total blood propofol level at 5, 10, 15, and 20 min or the protein-unbound free propofol level at 5 min after the intravenous administration of propofol between the 3 groups. However, the minimum BIS was significantly lower and the time until the BIS exceeded 60 was significantly longer in the poly-VPA group. In the multivariate regression analysis, belonging to the poly-VPA group was found to be independently associated with the minimum BIS value and the time until the BIS exceeded 60. Clinical VPA therapy did not influence the pharmacokinetics of propofol. However, multi-drug therapy involving VPA might enhance the anesthetic effects of propofol.
Highlights
Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol
Propofol is the most commonly used intravenous anesthetic for achieving such behavioral control because the depth of anesthesia induced by propofol can be controlled to a greater degree than that induced by other anesthetics, and so propofol is widely used for sedation and inducing general anesthesia during dental treatment for patients with intellectual disabilities (ID)
To evaluate the effects of VPA therapy on the pharmacokinetics of propofol, we compared the total and protein-unbound free propofol levels seen after the administration of a single bolus of propofol among patients treated without VPA, patients treated with mono-VPA therapy, and patients treated with poly-VPA therapy
Summary
Some previous studies have indicated that valproate (VPA) might change the pharmacokinetics and enhance the effects of propofol. This would lead to a significant increase in the level of active propofol, which can act on the γ -aminobutyric acid (GABA)A receptor, in the central nervous system (CNS) Regarding this hypothesis, we have already shown that VPA increased the proportion of protein-unbound free propofol in an in vitro study[8]. In previous in vitro studies, it was demonstrated that VPA inhibited propofol-metabolizing enzymes, such as cytochrome P-450 (CYP) 2C99 and UDP-glucuronosyltransferase (UGT) 1A910 This suggests that VPA might inhibit propofol metabolism and increase the level of propofol in the blood. Regarding the mechanism responsible for the effects of VPA, it is considered that VPA increase the levels of GABA in the CNS by inhibiting GABA transaminase[11] This process might enhance the activity of propofol, which is mostly mediated via the upregulation of GABA-induced chloride currents. We examined the differences in the propofol blood level, the protein-unbound free propofol level, and the bispectral index (BIS) seen after the administration of propofol between patients that were and were not treated with VPA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
