Pharmacokinetic and tolerance evaluation of actisomide, a new antiarrhythmic agent, in healthy volunteers.

The pharmacokinetics and tolerance of actisomide (SC-36602) were determined following intravenous doses of 2.1, 4.2, and 8.4 mg/kg infused over five hours. Plasma concentrations observed in the low-dose group (2.1 mg/kg) were below the assay's limit of detection and were not included in the pharmacokinetic analysis. The following pharmacokinetic parameters were obtained in the medium-dose (4.2 mg/kg) and high-dose (8.4 mg/kg) groups, respectively: peak plasma concentration 4.25 +/- 0.26 and 7.81 +/- 0.31 micrograms/mL; area under the plasma concentration versus time curve 19.79 +/- 2.96 and 39.81 +/- 7.05 h.micrograms/mL; elimination rate constant of the beta phase 0.105 +/- 0.77 and 0.093 +/- 0.009 h(-1), and half-life 8.85 +/- 4.61 and 7.51 +/- 0.69 h. Left ventricular ejection fraction decreased by 10, 11, and 16 percent in the low-, medium-, and high-dose groups, respectively. Heart rate was not altered during the low-dose infusion. At the medium- and high-dose levels, resting peak heart rate increased by 18 and 27 percent, respectively. Systolic and diastolic blood pressures were not significantly changed in any of the dose groups. Changes in electrocardiographic intervals for the three dose groups were not significant except at the highest dose where an average 20 percent increase in the QRS interval was seen. Mild subjective adverse effects (dizziness, taste perversion, and circumoral paresthesia) which did not necessitate discontinuing the infusion occurred in the highest dosage group. Further studies are warranted to more fully characterize the pharmacokinetic profile and therapeutic potential of actisomide.