Disopyramide, enantiomer interaction

J. J. Lima, Interaction of disopyramide enantiomers for sites on plasma protein. Life Sci., 41 2807 (1987). 

Identical chemical and physical properties of enantiomers represent a potential source for enantiomer-enantiomer interactions at both pharmacokinetic and pharmacodynamic levels. Whether by competition for plasma- or tissue-binding sites or for drug-metabolizing enzymes, enantiomers may exhibit changes in pharmacokinetics when administered as a racemate compared to individual stereoisomers. The enantiomers of disopyramide exhibit similar clearance and volumes of distribution when given separately. " However, when administered as the racemate, the 5... 

Some of the macrolide antibiotics have been reported to inhibit the clearance of disopyramide (SEDA-21, 200) (SEDA-22, 207), resulting in serious dysrhythmias or hypoglycemia. The mechanism of this interaction is presumed to be inhibition of dealkylation of disopyramide to its major metabolite, mono-A-dealkyldisopyramide. For example, in human liver microsomes the macrolide antibiotic troleandomycin significantly inhibited the mono-A-dealkylation of disopyramide enantiomers by inhibition of CYP3A4 (34). This interaction can result in serious dysrhythmias or other adverse effects of disopyramide. 

H. Takahashi, H. Ogata, and Y. Seki, Binding interaction between enantiomers of disopyramide and mono-N-dealkyldisopyramide on plasma protein, Drug Melab. Dispos., 19 554 (1991). 

Giacomini,K.M. Nelson, W.L. Pershe,R. A. Valdivieso,L. Turner-Tamiyasu, K. Blaschke, T.F. In vivo interaction of the enantiomers of disopyramide in human subjects. J. Pharmacokinet. Biopharm. 1986,14,335-356. 

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