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Sanjeev Kumar
Sanjeev Kumar
Tanzania
Publications
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Research Article
Atypical Kinetics of Valproic Acid Glucuronidation In vitro and In vivo in Humans
Author(s): Harvey Wong, Binfeng Xia, Vincent Tong, Sanjeev Kumar and Jane R KennyHarvey Wong, Binfeng Xia, Vincent Tong, Sanjeev Kumar and Jane R Kenny
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 Vmax app (39.5 ± 3.3 pmol/min/106 cells), S50 app (224 ± 34 µM) and n (2.34 ± 0.28) was obtained by fitting VPA-glucuronide formation rate vs VPA incubation concentration data to the Hill equation. In vitro EadieHofstee plots were “hooked” and characteristic of atypical sigmoidal/autoactivation kinetics. In vivo Eadie-Hofstee plots of VPA-glucuronide formation rate (calculated from urinary excretion rate data for VPA-glucuronide) were constructed using data fro.. View More»
DOI: 10.4172/2153-2435.S11-006