Title: Stereoselective de-ethylation of chloroquine in rat liver microsomes
Authors: Augustijns, Patrick ×
Peeters, L
Croes, K
Verbeeck, RK #
Issue Date: Jan-1999
Publisher: Medecine et hygiene
Series Title: European journal of drug metabolism and pharmacokinetics vol:24 issue:1 pages:105-108
Abstract: A qualitative kinetic study on the stereoselective hepatic metabolism of chloroquine was undertaken by separately incubating chloroquine enantiomers with rat liver microsomes. The dependency of desethylchloroquine formation on NADPH suggests a cytochrome P-450 isozyme catalysed metabolism. Over a wide concentration range (1-300 mu M), chloroquine metabolism appeared not to follow simple Michaelis-Menten kinetics. The enantiomeric ratio (R/S) of desethylchloroquine was dependent on concentration, and ranged from 8 at 1 mu M to 1 at 300 mu M. Mutual enantiomer-enantiomer interaction studies at low concentration (1-5 mu M) revealed that the formation of (R)-desethylchloroquine was strongly inhibited by (S)-chloroquine. The findings of the present study support the hypothesis that a high-affinity/low capacity enzyme is capable of stereoselective discrimination. At this point, it remains to be proven whether stereoselective metabolism and enantiomer-enantiomer interactions affect the in vivo disposition of chloroquine.
ISSN: 0378-7966
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
× corresponding author
# (joint) last author

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