LACK OF EFFECT OF MIZOLASTINE ON THE SAFETY AND PHARMACOKINETICS OF DIGOXIN ADMINISTERED ORALLY IN REPEATED DOSES TO HEALTHY-VOLUNTEERS

The effects of mizolatine, a new H-1 receptor antagonist, on safety an d pharmacokinetics of digoxin were studied in a double-blind placebo-c ontrolled crossover study. After administration of digoxine alone (0.2 5 mg o.d. for 7 days), 12 healthy young male volunteers (23 +/- 2 year s) received either placebo and digoxin (0.25 mg od) or mizolastine (10 mg o.d.) and digoxin (0.25 mg o.d.) during 7 days. The assessment cri teria consisted in hemodynamic and ECG parameters recordings and the p harmacokinetics of digoxin during the last day of coadministration (da y 14). No difference between the 2 treatment groups was evidenced on E GG, hemodynamic, and clinical and laboratory safety parameters. No cha nge in AUC and t(max) was recorded. No clinically relevant effect of m izolastine on the digoxin pharmacokinetics was found. However, a stati sticallly significant increase in digoxin C-max (3.03 +/- 0.18 nmolxl( -1) vs 2.52 +/- 0.19 nmolxl(-1), p < 0.05) and C-min (0.99 +/- 0.08 nm olxl(-1) vs 0.87 +/- 0.07 nmolxl(-1), p = 0.05) occurred after the coa dministration vs digoxin alone. It can be concluded that mizolastine a nd digoxin at therapeutic dosages can be safely coadministered.