Effect of deuteration on the metabolism and clearance of some pharmacologically active compounds--synthesis and in vitro metabolism of deuterated derivatives of dronedadrone

Joseph Schofield; Denis Brasseur; Béatrice de Bruin; Thierry Vassal; Sylvie Klieber; Catherine Arabeyre; Martine Bourrié; Freddy Sadoun; Gérard Fabre

doi:10.1002/jlcr.3090

Effect of deuteration on the metabolism and clearance of some pharmacologically active compounds--synthesis and in vitro metabolism of deuterated derivatives of dronedadrone

J Labelled Comp Radiopharm. 2013 Jul-Aug;56(9-10):504-12. doi: 10.1002/jlcr.3090. Epub 2013 Sep 4.

Authors

Joseph Schofield¹, Denis Brasseur, Béatrice de Bruin, Thierry Vassal, Sylvie Klieber, Catherine Arabeyre, Martine Bourrié, Freddy Sadoun, Gérard Fabre

Affiliation

¹ Isotope Chemistry and Metabolite Synthesis, DSAR-DD, Sanofi R&D, 1 Avenue Pierre Brossolette, 91380, Chilly-Mazarin, France.

PMID: 24285529
DOI: 10.1002/jlcr.3090

Abstract

The synthesis and in vitro metabolism studies of a family of specifically deuterated derivatives of dronedarone are described. Metabolic stability and clearance of the parent compound are not sensitive to deuterium substitution, irrespective of the position of the heavy label.

Keywords: antiarrhythmic; deuterium; deuterium labelling; in vitro metabolism; isotope effect; stable labelled synthesis.

MeSH terms

Amiodarone / analogs & derivatives*
Amiodarone / chemical synthesis
Amiodarone / chemistry
Amiodarone / metabolism
Chemistry Techniques, Synthetic
Deuterium / chemistry*
Dronedarone
Hepatocytes / metabolism
Humans
Structure-Activity Relationship

Substances

Deuterium
Dronedarone
Amiodarone