Serum binding of tocainide and its enantiomers in human subjects.

Serum from five healthy male volunteers aged 25-36 years was dialyzed against a series of buffer solutions containing varying amounts of racemic tocainide. The concentration of each enantiomer of the drug in the post-dialysis buffer and serum was determined using a specific gas-liquid-chromatographic method. The concentration of total tocainide in the post-dialysis sera ranged from 1.16 to 19.73 micrograms/ml. The percentage of total unbound tocainide ranged from 84.9 +/- 3.3 to 89.9 +/- 2.2 (mean +/- S.D.) whereas the percentages of unbound R-(-) and S-(+) enantiomers ranged from 86.3 +/- 4.0 to 91.0 +/- 2.3 and 83.3 +/- 5.4 to 88.9 +/- 2.2 respectively. Although the binding of the S-(+) enantiomer was slightly but statistically significantly greater than that of the R-(-) isomer, the difference would be of little clinical significance. Binding appeared independent of serum tocainide concentration within the therapeutic range of 4 to 12 micrograms/ml.