Use of hexadeuterated valproic acid and gas chromatography-mass spectrometry to determine the pharmacokinetics of valproic acid

Journal Article · Sun Apr 01 00:00:00 EST 1984 · J. Pharm. Sci.; (United States)

DOI:https://doi.org/10.1002/jps.2600730415· OSTI ID:6312594

Acheampong, A A; Abbott, F S; Orr, J M; Ferguson, S M; Burton, R W

Di-(( 3,3,3-/sup 2/H3)propyl)acetic acid, a hexadeuterated analogue of valproic acid, was synthesized and its pharmacokinetic properties compared with valproic acid. Concentrations of valproic acid and (/sup 2/H)valproic acid in serum and saliva were determined by GC-MS using selected-ion monitoring. Saliva drug levels were measured with good precision down to 0.1 microgram/mL. Kinetic equivalence of valproic acid and (/sup 2/H)valproic acid was demonstrated in a single-dose study in a human volunteer. An isotope effect was observed for omega-oxidation, but the difference in metabolism was not sufficient to make (/sup 2/H)valproic acid biologically nonequivalent. The application of (/sup 2/H)valproic acid to determine the kinetics of valproic acid under steady-state concentrations was evaluated in the same volunteer. The kinetic data obtained with (/sup 2/H)valproic acid was consistent with previously reported values for valproic acid including kinetic differences observed between single-dose and steady-state experiments. Saliva levels of valproic acid were found to give a good correlation with total serum valproic acid under multiple-dose conditions. A concentration dependence was found for the ratio of saliva valproic acid to free valproic acid in serum, low ratios being observed at high serum concentrations of valproic acid.

• Research Organization: Univ. of British Columbia, Vancouver, Canada
• OSTI ID: 6312594
• Journal Information: J. Pharm. Sci.; (United States), Vol. 73:4
• Country of Publication: United States
• Language: English

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38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
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DEUTERIUM COMPOUNDS
TRACER TECHNIQUES
RADIOPHARMACEUTICALS
CHEMICAL PROPERTIES
BLOOD SERUM
GAS CHROMATOGRAPHY
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MATERIALS
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