OBJECTIVE

To evaluate safety and tolerance of single or repeated doses of domestic antiarrhythmic agent class III tablets in healthy volunteers.

MATERIAL AND METHODS

Healthy men aged 18—45 years were divided into 6 cohorts: single oral dose 1, 2, 4 and 6 mg, 1 mg IV (6 ones in each cohort), 2 mg daily for 5 days (11 patients). Drug intake/injection, blood and urine tests, blood sampling for pharmacokinetic analysis, assessment of vital signs, ECG registration and 24-hour ECG monitoring were performed in a hospital.

RESULTS

The study included 41 patients aged 32±7.6 years (mean weight 74.6±4.7 kg). No significant changes of blood and urine tests, as well as vital signs were registered in any cohort. Single oral dose 6 mg significantly increased QT and QTc intervals. Multiple intake of 2 mg significantly increased QT/QTc intervals with maximum increment after 4—5 days.

CONCLUSION

Single oral intake of various doses of Refralon and multiple intakes of 2 mg daily maintain QT/QTc intervals within the reference values throughout the entire follow-up period. Significant persistent prolongation of QT/QTc intervals is noted only when taking the maximum dose of 6 mg once and repeated doses of 2 mg.