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Bilastine (tradename Bilaxten) is an H1 antihistamine antagonist used to treat rhinoconjunctivitis (seasonal and perennial) and urticaria. It has a potency similar to cetirizine and is superior to fexofenadine.

The drug was developed in Spain by FAES Farma and recently approved in 28 countries of the European Union (EU) for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It meets the current European Academy of Allergy and Clinical Immunology (EAACI) and Allergic Rhinitis and its Impact of Asthma (ARIA) criteria for medication used in the treatment of allergic rhinitis.

Bilastine has been effective in the treatment of ocular symptoms and diseases of allergies, including rhinoconjuctivitis. Additionally, bilastine has been shown to improve quality of life, and all nasal and ocular symptoms related to allergic rhinitis.

Chemistry
Bilastine, or 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazol-2-yl] piperidin-1-yl] ethyl] phenyl]-2-methylpropionic acid, is a novel molecule with a molecular weight of 463.6 daltons and a chemical structure similar to piperidinyl-benzimidazole. Bilastine can be therefore classified into the same chemical group as many of the new antihistamines on the market, although it is not structurally derived, nor is it a metabolite or enantiomer of any of them, but an original molecule designed with the intent of fulfiling all the requirements of a second-generation antihistamine.

Dosage
A therapeutic dosage of bilastine is 20mg once a day orally and shows a rapid onset of action (within 30-60 mintues). It should be taken only by children older than 12 years and adults.

Pharmacodynamics
Bilastine binds to H1-receptors to human recombinant H1-receptors with an affinity comparable to that of astemizole and diphenhydramine, and superior than that of cetirizine by three-fold and fexofenadine by five-fold (Corcóstegui). In different murine models, bilastine antagonizes the effects of histamine in a concentration-dependent manner, with potency similar to that of fexofenadine and between 5.5- and 10-times greater than that of cetirizine.

Preclinical investigations demonstrate the affinity and specificity of bilastine for H1-receptors compared with other histamine receptors and other receptor subtypes. In vivo experimentation confirmed the antihistaminic and antiallergic activity, which was at least comparable to that of other second-generation H1-antihistamines such as cetirizine or fexofenadine.

Clinical studies using different dosages were done on histamine-induced wheal and flare reaction over a 24-h period, compared with a single 10-mg oral dose of cetirizine. The results of this research indicated that bilastine was at least as efficient as cetirizine in reducing histamine-mediated effects in healthy volunteers. Remarkably, 20 and 50 mg of bilastine reduced the wheal and flare reaction significantly more quickly than cetirizine.

Distribution
Bilastine distribution has an apparent volume of distribution of 1.29 l/kg, and has an elimination half-life of 14.5 h and plasma protein binding of 84-90%.

Absorption & bioavailability
Bilastine is most quickly absorbed with the absence of food, and reaches a mean peak plasma concentration (Cmax ) of 220 ng/ml approximately 1 h after both single and multiple dosing. Absorption is reduced by a high-fat breakfast or fruit juice, and the estimated global oral bioavailability is approximately 60% Bilastine has linear pharmacokinetics in the 2.5-220-mg dose range in healthy adult subjects without evidence of accumulation after 14 days of treatment.

Metabolism
Bilastine is not significantly metabolized in humans and is largely eliminated unchanged both in urine and feces - a third and two thirds of the administered dose, respectively, according to a Phase I mass-balance study with radiolabeled bilastine. Bilastine does not readily cross the blood brain barrier and is not metabolized by the liver. 96% of the administered dose is eliminated within 24 hours.

In relation to it's antihistamine effect, oral doses of 20 mg daily of bilastine, measured as skin wheal-and-flare surface areas for 24 h, bilastine is capable of inhibiting 50% of the surface areas - throughout the whole administration interval.

Drug interactions & food effects
Preclinical data suggest the possibility of interactions between bilastine and drugs or food that are inhibitors or inducers of the P-glycoproteins. Coadministration of bilastine and grapefruit juice (a known P-glycoprotein-mediated drug transport activator) significantly reduced bilastine systemic exposure. This interaction is due to the known effect of grapefruit flavonoids on intestinal transporter systems such as P-glycoproteins and organic anion transporting peptide (OATP).

Safety & tolerability
Toxicity of bilastine investigated in preclinical toxicology studies in mice, rats and dogs after oral and intravenous administration showed no mortality observed after oral administration of massive doses. After intravenous administration, LD50 (lethal dose for 50% of animals) values were 33 and 45-75 mg/kg in mice and rats, respectively. No signs of toxicity were observed in any organ after bilastine massive overdosing, either orally (in mice, rats and dogs), or intravenously (in rats and dogs) during 4 weeks. No effects on fertility, no teratogenic or mutagenic effects, and no apparent carcinogenic potential were seen in the studies carried out in rats, mice and rabbits.

In clinical research, bilastine has proven to be well tolerated, with an adverse events profile similar to that of placebo in healthy volunteers, patients with AR and with chronic idiopathic urticaria. Although the tolerance profile of bilastine and levocetirizine or desloratadine were very similar, bilastine was markedly better tolerated than cetirizine in a clinical assay in SAR [36] , with fewer adverse events in the bilastine group. No anticholinergic adverse events were observed in the clinical trials with bilastine. No serious adverse events were reported during the research and there were no clinically significant changes in vital signs, ECG or laboratory tests. Pharmacokinetic/pharmacodynamic profiles and studies in special populations indicate that bilastine as dose adjustment is not necessary in elderly patients, or in hepatic or renal insufficiency.

Side Effects
Bilastine has been shown to have no adverse cardiac side effects, and does not affect driving ability, cardiac conduction or alertness. Possible side effects include headache and drowsiness. Uncommon side effects (affects 1 to 10 users in 1,000), include abnormal ECG heart tracing, blood tests which show changes in the way the liver is working, dizziness, stomach pain, tiredness, increased appetite, irregular heartbeat, increased weight, nausea (the feeling of being sick), anxiety, dry or uncomfortable nose, belly pain, diarrhea, gastritis (inflammation of the stomach wall), vertigo (a feeling of dizziness or spinning), feeling of weakness, thirst, dyspnoea (difficulty in breathing ), dry mouth, indigestion, itching, cold sores (oral herpes), fever, tinnitus (ringing in the ears), difficulty in sleeping, blood tests which show changes in the way kidney is working, and increased blood fats.