Pharmacokinetics, Pharmacodynamics and Population Pharmacokinetic/Pharmacodynamic Modelling of Bilastine, a Second-Generation Antihistamine, in Healthy Japanese Subjects

Abstract

Background and objectivesBilastine is a novel second-generation antihistamine for the symptomatic treatment of allergic rhinitis and urticaria. The objective of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of bilastine following single and multiple oral doses in healthy Japanese subjects. The pharmacokinetic and pharmacodynamic profiles were compared with those reported in Caucasian subjects.MethodsIn a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study, bilastine tablets were administered at single doses of 10, 20, and 50 mg (Part I), and once daily for 14 days at 20 and 50 mg (Part II).ResultsAfter single oral doses, maximum plasma concentrations (C max) were reached at 1.0–1.5 h postdose. Plasma exposure [C max and area under the plasma concentration-time curve (AUC)] increased dose-proportionally at single doses of 10–50 mg. In repeated-dose administration, no remarkable differences were observed between Day 1 and Day 14 for C max or AUC. For inhibitory effects on wheal and flare response, bilastine 20 and 50 mg showed significant inhibition from 1.5 h after administration as compared with placebo, and the significant effect persisted for 24 h after administration. The rates of adverse events (AEs) were comparable between bilastine and placebo in both Part I and Part II. In addition, no dose- or administration period-dependent tendency of increase in rate of AEs or worsening of severity was observed.ConclusionBilastine exhibits similar single- and multiple-dose pharmacokinetic and pharmacodynamic characteristics in healthy Japanese subjects compared with those observed in Caucasian subjects in previous studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s40261-016-0447-2) contains supplementary material, which is available to authorized users.

Bilastine: a lifetime companion for the treatment of allergies

“…Bilastine has high specificity for H 1 -receptors and negligible affinity for other receptors, and demonstrates antihistamine and antiallergic properties 10,11 . Bilastine has a rapid onset of action and a long duration of action [12][13][14][15] . It has been shown to have a long residence time at the H 1receptor, resulting in prolonged receptor antagonism, with 60-70% antagonism evident 24 hours after dosing 8 .…”

“…Bilastine is administered orally once daily. It is rapidly absorbed after oral administration, achieving maximum plasma concentrations after 1-1.5 hours 12,15,16 . Concurrent food intake reduces the bioavailability of bilastine.…”

“…It does not undergo significant hepatic metabolism and approximately 95% is excreted unchanged in either the faeces (67%) or urine (33%) 19 . Bilastine has a mean elimination half-life of approximately 12-14.5 hours 8,12,15,17 . No dosage adjustments are required in patients with renal or hepatic impairment or in elderly people 18,20 .…”

“…The practical message for physicians is to "keep it simple". Antihistamines that can be administered once daily and have a rapid onset of action, such as bilastine 12,13,15,18 , are a practical option for patients with allergic rhinitis.…”

“…Studies in healthy adult volunteers showed that bilastine suppressed the wheal and flare response compared with placebo and that it had a rapid onset of action, with a high level of inhibition evident after 0.5-2 hours 14,15,42 . Bilastine had a faster onset of action than cetirizine, desloratadine and rupatadine 13,14 .…”