Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs.

@article{Sharma2012DeuteriumIE,
  title={Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs.},
  author={Raman R Sharma and Timothy J Strelevitz and Hongying Gao and Alan J Clark and Klaas Schildknegt and R Scott Obach and Sharon L. Ripp and Douglas K Spracklin and Larry M. Tremaine and Alfin D. N. Vaz},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2012},
  volume={40 3},
  pages={625-34}
}
The pharmacokinetic properties of drugs may be altered by kinetic deuterium isotope effects. With specifically deuterated model substrates and drugs metabolized by aldehyde oxidase, we demonstrate how knowledge of the enzyme's reaction mechanism, species differences in the role played by other enzymes in a drug's metabolic clearance, and differences in systemic clearance mechanisms are critically important for the pharmacokinetic application of deuterium isotope effects. Ex vivo methods to… CONTINUE READING
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