Res Commun Chem Pathol Pharmacol. 1985 Jul;49(1):109-24.  

Kinetics of microsomal metabolism of quinidine in rats.

Rakhit A, Mico B.

Kinetics of in vitro metabolism of quinidine was investigated using rat liver
microsomes. Quinidine elimination was capacity limited with apparent Michaelis
constant (appKM) of 2.6 microM (about 1.2 mg/L) in liver microsomes from
uninduced rats. Phenobarbital (PB) pretreatment caused induction of quinidine
metabolism. Formation of all three metabolites important in man,
3-hydroxyquinidine, quinidine N-oxide and quinidine 10,11-dihydrodiol were PB
inducible (Vmax increased). To study any direct interaction between PB and
quinidine, PB was also added to the microsomal incubate and was found to
decrease the rate constant for quinidine metabolism, suggesting inhibition of
quinidine metabolism by PB. While, 3-hydroxyquinidine formation was inhibited
(Vmax decreased and KM increased), the formation of quinidine N-oxide was
activated (Vmax increased). The formation of quinidine 10,11-dihydrodiol,
although a minor metabolite in rat, was also inhibited in presence of PB. It is
apparent from this study that PB when administered in vivo would act as both
inducer and inhibitor of quinidine metabolism.

PMID: 4035074 [PubMed - indexed for MEDLINE]