Comparison of electrocardiographic response and disposition of R- and S-disopyramide in the rabbit.

Both R- and S-disopyramide prolong the QRS interval of the electrocardiogram in the rabbit. R-disopyramide is more potent than S-disopyramide at high concentrations (greater than 6 micrograms/ml), but shows similar potency at low concentrations (less than 6 micrograms/ml). R-disopyramide shows an estimated intermediate hepatic extraction ratio with a plasma clearance of 31.0 +/- 3.2 ml/min/kg that is only to a small degree concentration-dependent. S-disopyramide plasma clearance, on the other hand, is highly concentration-dependent, with a value larger than 50 ml/min/kg at concentrations below 4 micrograms/ml, that decreases to a value of approximately 30 ml/min/kg at 16 micrograms/ml. No differences in the binding of R- and S-disopyramide to rabbit serum or rabbit serum spiked with human alpha 1-acid glycoprotein were found.