Pharmacodynamics and pharmacokinetics of mizolastine (SL 85.0324), a new nonsedative H1 antihistamine.
The antihistaminic activity, clinical safety, and pharmacokinetics of mizolastine (SL 85.0324) were studied in a 5-way, double-blind crossover study of ten healthy volunteers with doses of 1 to 75 mg. Inhibition of the histamine-induced wheal and flare showed clear dose-dependent antihistaminic activity beginning from the 2-mg dose with a maximum attained between 10 and 20 mg. The onset of action was rapid (one hour) and the effect persisted for more than 24 hours after a 10-mg dose or more. Mizolastine was well tolerated at doses up to 75 mg; subjective and objective signs of transient sedative activity were not observed at doses below 30 mg. The pharmacokinetic profile (rapid absorption with Tmax congruent to 1 h and elimination T1/2 of about eight hours) parallels the pharmacodynamic activity. Within the considered dose range, the pharmacokinetics was linear with no saturation phenomena.
Rosenzweig
P
P
Synthélabo Recherche, Bagneux, France.
Thebault
J J
JJ
Caplain
H
H
Dubruc
C
C
Bianchetti
G
G
Fuseau
E
E
Morselli
P L
PL
D000328:Adult; D001562:Benzimidazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011594:Psychometrics; D012894:Sleep Stages
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; C076170:mizolastine