H. Riethmullerwinzen et al., TOLERABILITY, PHARMACOKINETICS AND DOSE LINEARITY OF AZELASTINE HYDROCHLORIDE IN HEALTHY-SUBJECTS, Arzneimittel-Forschung, 44-2(10), 1994, pp. 1136-1140
In a double-blind randomized, 4-period crossover study, single oral do
ses of azelastine hydrochloride tablets (A-05610, Allergodil(R), Radet
hazin(R), Azeptin(R), CAS 79307-93-0) were ingested by 12 healthy volu
nteers (6 males, 6 females, mean age 25.2 +/- 3.5 years). Dose lineari
ty was demonstrated for 2.2, 4.4, 8.8 and 17.6 mg of azelastine hydroc
hloride. The values of AUC(0-infinity) and C-max increased linear to t
he dose (means of AUC(0-infinity): 47.3, 93.7, 208.0 and 405.90 ng-eq
h/ml; means of C-max: 1.5, 3.3, 6.0 and 12.5 ng-eq/ml), whereas t(max)
and the terminal half-life of elimination (t(1/2 beta) ) were obvious
ly not influenced by the dose Mean values over all doses and subjects
amounted to 4.6 h (t(max)) and 25.5 h (t(1/2 beta)). Plasma levels sho
wed relatively high inter- and somewhat less intraindividual variation
s. This is most likely due to a varying degree of enterohepatic circul
ation resulting from alimentary factors. As for the co-detection of az
elastine and the pharmacodynamically active metabolite N-desmethyl-aze
lastine by the radio-immunoassay (RIA) used the parameters describe th
e pharmacokinetic behaviour as a resultant from both compounds and thu
s the active principle of the drug. Independently of the dosages admin
istered the overall tolerance proved to be very good. According to thi
s trial the therapeutic range is wide enough to recommend 4.4 mg b.i.d
or single doses of 8.8 mg of azelastine hydrochloride per day for the
rapy in adult patients.