Atypical Kinetics of Valproic Acid Glucuronidation In vitro and In vivo in Humans

Harvey Wong, Binfeng Xia, Vincent Tong
2012 Pharmaceutica Analytica Acta  
Atypical kinetics has been observed in vitro for both cytochrome P450 and UDP-glucuronosyltransferase catalyzed enzymatic reactions. The in vitro and in vivo kinetics of valproic acid-glucuronide (VPA-glucuronide) formation was investigated in humans. VPA-glucuronide formation kinetics was investigated in vitro using human cryoperserved hepatocytes (pool of 10). Estimates of V max app (39.5 ± 3.3 pmol/min/10 6 cells), S 50 app (224 ± 34 µM) and n (2.34 ± 0.28) was obtained by fitting
more » ... nide formation rate vs VPA incubation concentration data to the Hill equation. In vitro Eadie-Hofstee plots were "hooked" and characteristic of atypical sigmoidal/autoactivation kinetics.
doi:10.4172/2153-2435.s11-006 fatcat:4lchymj6nrfo5ct7q5owcyn3le