TOLERABILITY, PHARMACOKINETICS AND DOSE LINEARITY OF AZELASTINE HYDROCHLORIDE IN HEALTHY-SUBJECTS

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.