Abstract
The effect of fasting and glucose-infusion on valproate (VPA) disposition was investigated to determine the involvement of endogenous fatty acid (FA) beta-oxidation in the metabolism of VPA. Fifteen healthy volunteers received multiple oral doses of VPA to achieve steady state under both conditions. Depressed plasma FA concentrations in the glucose-infused state (median 51%, p less than 0.0001) were associated with lower unbound plasma VPA fractions (median 17%, p less than 0.0001). Unbound plasma VPA concentrations were notably lower in the glucose-infused state due to significantly higher (median 41%, p less than 0.0001) metabolic clearance, beta-oxidative metabolite formation clearance, representing the largest urinary dose fraction recovered, was significantly higher (median 60%, p less than 0.004) in the glucose-infused state. This finding is consistent with competition between endogenous FA and VPA for the enzymes of beta-oxidation modulated by conditions which affect FA mobilization to the site of catabolism.
Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
