The use and limitations of deuterated lorcainide in metabolism and pharmacokinetic studies

Lorcainide, a new antiarrhythmic agent currently undergoing clinical trial, has been pentadeuterated and the usefulness of this labelled compound in pharmacokinetic and metabolism studies has been investigated in dogs. Specific analytical methods based on capillary gas chromatography/mass spectrometry (GC/MS) were developed for quantitative and qualitative analysis of plasma and urine samples. Following oral administration of an equimolar mixture of 5 : 5 mg of (2H0/2H5)lorcainide, eight major metabolites were rapidly identified in urine by the ion cluster technique. Quantitative analysis of (2H0/2H5)lorcainide in plasma and urine indicated an enhanced systematic availability of the deuterated compound, probably due to a secondary isotope effect. According to these findings in the dog, the use of deuterated lorcainide in human bioavailability and metabolism studies is probably of limited value.