Pharmacokinetics and pharmacodynamics of the novel H-1-receptor antagonistemedastine in healthy volunteers

Objective: Emedastine is a novel H-1-receptor antagonist with pre-clinicall y well-documented antiallergic effects. Here, we set out to study the relat ionship between emedastine pharmacokinetics and the suppressive effect on h istamine-induced wheals and flares, and to compare these effects to placebo and cetirizine. Methods: Emedastine (4 mg q.d.), emedastine (2 mg b.i.d.), cetirizine (10 m g q.d.) and placebo were administered to healthy volunteers in a double-bli nd, cross-over fashion. On day 1 and day 5 (steady state) following drug ad ministration, wheals and flares were induced by skin-prick testing with 1 m g ml(-1) or 10 mg ml(-1) histamine. Results: Following the administration of 4 mg emedastine q.d., mean area un der the concentration-time curve (AUC)(0-24) values of 34.49 +/- 24.07 ng h ml(-1) and 47.05 +/- 36.12 ng h ml(-1) were attained on day 1 and day 5, r espectively. Following the administration of emedastine (2 mg b.i.d.) mean AUC(0-24) values were 29.75 +/- 19.92 ng h ml(-1) and 46.13 +/- 38.50 ng h ml(-1) on day 1 and day 5, respectively. Histamine-induced wheals and hares were significantly more effectively suppressed by emedastine and cetirizin e than placebo. At pharmacokinetic steady-state levels, no significant diff erence could be found in the potency between cetirizine and emedastine (2 m g b.i.d.). Conclusion. Emedastine displays pharmacodynamic properties comparable with cetirizine and therefore qualifies as a safe and alternative compound with H-1-receptor antagonist properties. Additional larger studies may be needed to substantiate potential benefits of cetirizine over emedastine after sin gle-dose administration.