LACK OF RELATIONSHIP BETWEEN QUINIDINE PHARMACOKINETICS AND THE SPARTEINE OXIDATION POLYMORPHISM

Quinidine is a very potent inhibitor of CYP2D6, but the role of the en zyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to prese nt definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of spar teine each took one oral dose of 200 mg quinidine. In the EM, the tota l clearance, the clearance via 3-hydroxylation and the clearance via N -oxidation, were 33, 3.7 and 0.231 . h(-1), respectively. In the PM, t he corresponding values were 29, 3.1 and 0.181 . h(-1), respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D 6 is not an important enzyme for the oxidation of quinidine.