Pharmacokinetics and pharmacodynamics of the novel H1-receptor antagonist emedastine in healthy volunteers.
OBJECTIVE
Emedastine is a novel H1-receptor antagonist with pre-clinically well-documented anti-allergic effects. Here, we set out to study the relationship between emedastine pharmacokinetics and the suppressive effect on histamine-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 mg q.d.) and placebo were administered to healthy volunteers in a double-blind, cross-over fashion. On day 1 and day 5 (steady state) following drug administration, wheals and flares were induced by skin-prick testing with 1 mg ml(-1) or 10 mg ml(-1) histamine.


RESULTS
Following the administration of 4 mg emedastine q.d., mean area under 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, respectively. Following the administration of emedastine (2 mg b.i.d.) mean AUC0-24 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 flares were significantly more effectively suppressed by emedastine and cetirizine than placebo. At pharmacokinetic steady-state levels, no significant difference could be found in the potency between cetirizine and emedastine (2 mg b.i.d.).


CONCLUSIONS
Emedastine displays pharmacodynamic properties comparable with cetirizine and therefore qualifies as a safe and alternative compound with H1-receptor antagonist properties. Additional larger studies may be needed to substantiate potential benefits of cetirizine over emedastine after single-dose administration.
Jansen
B
B
Department of Clinical Pharmacology, University of Vienna, Austria.
Graselli
U
U
Dallinger
S
S
Kiss
B
B
Wacheck
V
V
Schlagbauer-Wadl
H
H
Assandri
A
A
Müller
M
M
D000328:Adult; D019540:Area Under Curve; D001562:Benzimidazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D017332:Cetirizine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006632:Histamine / Q000009:adverse effects; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D012882:Skin Tests; D012894:Sleep Stages / Q000187:drug effects
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D006632:Histamine; C043345:emedastine; D017332:Cetirizine