Bilastine

Last updated
Bilastine
Bilastine.svg
Clinical data
Trade names Blexten, others
Pregnancy
category
Routes of
administration 		By mouth
Drug class Antihistamine
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 61% [1]
Protein binding 84-90% binding to plasma proteins [1]
Metabolism Not significantly metabolised [1]
Onset of action 1 hour (Allertine) [1]
Elimination half-life 14.5 hours [1]
Duration of action 24 hours (Allertine) [1]
Excretion 95% in urine and faeces [1]
Identifiers
  • 2-[4-(2-{4-[1-(2-Ethoxyethyl)-1H-benzimidazol-2-yl]-1-piperidinyl}ethyl)phenyl]-2-methylpropanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.260.016 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C28H37N3O3
Molar mass 463.622 g·mol−1
3D model (JSmol)
  • O=C(O)C(c1ccc(cc1)CCN4CCC(c2nc3ccccc3n2CCOCC)CC4)(C)C
  • InChI=1S/C28H37N3O3/c1-4-34-20-19-31-25-8-6-5-7-24(25)29-26(31)22-14-17-30(18-15-22)16-13-21-9-11-23(12-10-21)28(2,3)27(32)33/h5-12,22H,4,13-20H2,1-3H3,(H,32,33) Yes check.svgY
  • Key:ACCMWZWAEFYUGZ-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Bilastine is an antihistamine medication used to treat hives (urticaria), allergic rhinitis and itchy inflamed eyes (allergic conjunctivitis) caused by an allergy. [4] It is a second-generation antihistamine and takes effect by selectively inhibiting the histamine H1 receptor, preventing these allergic reactions. [5] Bilastine has an effectiveness similar to cetirizine, fexofenadine, and desloratadine. [6]

Contents

Bilastine is approved in the European Union for the symptomatic treatment of allergic conjunctivitis and urticaria. [7] It is not approved for any use in the United States. [8]

Evidence has shown that bilastine is effective in treating skin and eye symptoms of allergic reactions, improving patient's quality of life. [6] [9] Bilastine meets the treatment criteria for allergic rhinitis, as published by the European Academy of Allergy and Clinical Immunology (EAACI) and the Allergic Rhinitis and its Impact of Asthma (ARIA) initiative. [9]

Medical uses

Allergic rhinoconjunctivitis

The clinical efficacy of bilastine in allergic rhinitis (AR) and urticaria has been assessed in 10 clinical assays in which over 4,600 patients were involved. All of them compared bilastine with placebo and another second generation antihistamine with confirmed efficacy (active comparator).

Allergic rhinitis

The studies on SAR were double-blind, placebo-controlled, parallel-group involving male and female patients over 12 year of age with symptomatic disease at the beginning of the study. Nasal symptoms (sneezing, rhinorrhea, nasal itching and congestion) were assessed both before treatment and during treatment period on a daily basis. Non nasal symptoms (itchy eye, watery eye, itchy ear and palate) were also assessed according to a 0–3 scale, so that the Total Symptoms Score (TSS) and other related parameters could clearly reflect daily evolution of SAR in each patient and treatment group. Parameters such as quality of life and discomfort were also assessed, and in the same way the type and frequency of AE, tolerability and general safety of treatment were registered. In this SAR studies the daily oral administration during 14 days of bilastine proves to have the same efficacy as the administration of cetirizine and desloratadine. [10]

Urticaria

A review article evaluated data from trials which detailed the efficacy of bilastine in skin models and urticaria to assess whether bilastine has an optimal profile for updosing in urticaria. The authors concluded that bilastine has an excellent profile for both efficacy and safety, although there is a need for controlled clinical trials to compare the efficacy of bilastine in a real-life updosing study in patients with urticaria, paying special attention to itch control. [11]

Dosage and administration

Bilastine comes as a tablet taken by mouth (PO) and it is supposed to be swallowed whole with water. Bilastine should not be given with, or within 1 hour before or 2 hours after, food as it may reduce its effectiveness. Australian dosing guidelines for Allertine give a maximum dose of 20mg (one tablet) daily as needed (PRN). [12] Dose changes are not required for hepatic or renal impairment. [12]

While the onset of its effects vary between formulations, bilastine generally takes effect within 30–60 minutes. [6] It should be taken only by children older than 4 years and adults, or anyone over 12 years for Allertine. [9] [12]

Side effects

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. [13]

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, [14] bilastine was markedly better tolerated than cetirizine in a clinical assay in SAR, 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, electrocardiography (ECG) or laboratory tests. Pharmacokinetic/pharmacodynamic profiles and studies in special populations indicate that dose adjustment of bilastine is not necessary in elderly patients or in chronic liver disease or chronic kidney disease.

Cardiac safety

The clinical cardiac safety of bilastine has been assessed in many clinical trials performed [14] [15] [16] (more than 3,500 patients treated with bilastine) and in a phase I study (Thorough QT/QTc study) designed according to the ICH E14 guidance and the most demanding requirements from the Food and Drug Administration (FDA). [17] When electrocardiograms (ECG) data from all of the phase I studies are analysed, no significant alteration is appreciated in any of the parameters after administering bilastine at single doses (up to 11 times the therapeutic dose), nor at multiple doses (up to 10 times the therapeutic dose). Phase II and III studies on AR and urticaria (including the open-label extension phase of 12 months) do not reveal alterations in the ECG, nor significant prolongations of the QTc interval after administration of bilastine 20 mg.

The Thorough QT/QTc study was designed to assess the effect on the QT/QTc interval, both of the therapeutic dose (20 mg) and 100 mg of bilastine, but also the coadministration of the therapeutic dose with usual doses of ketoconazol (400 mg/day), a metabolism inhibitor and a P-gP dependent transport system. It was verified that bilastine 20 and 100 mg administered during 4 days, does not induce significant changes in the QT/QTc interval duration in any of the individuals. [16] [17] Likewise, coadministration of bilastine 20 mg and ketoconazol 400 mg does not produce any significant prolongation of the QT/QTc interval attributable to bilastine.

Interactions

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. [18] 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). [19]

Pharmacology

Pharmacodynamics

Bilastine binds to guinea-pig cerebellar histamine H1-receptors (Ki=44 nM) and to human recombinant histamine H1-receptors (Ki=64 nM) 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 by oral route, antagonizes the effects of histamine in a dose-dependent manner, with potency similar to that of cetirizine and between 5.5 and 10 times greater than that of fexofenadine. [20]

Preclinical investigations demonstrate the affinity and specificity of bilastine for histamine H1-receptors compared with other histamine receptors subtypes and other 30 receptors from different amines. 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. [6] [10]

Pharmacokinetics

Absorption

Bilastine is most quickly absorbed with the absence of food, and reaches a mean peak plasma concentration of 220 ng/mL approximately 1 h after both single and multiple dosing. [21] Absorption is reduced by a high-fat breakfast or fruit juice, and the estimated global oral bioavailability is approximately 60%. [21] 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. [21]

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%. [22]

Bilastine is a peripherally selective drug, and this thought to be due to limited brain uptake caused by binding to P-glycoprotein. [23] [24]

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. [25] Bilastine does not readily cross the blood brain barrier and is not metabolized by the liver. [21] Ninety six percent of the administered dose is eliminated within 24 hours. [21]

In relation to its 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. [21]

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. [21] 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 fulfilling all the requirements of a second-generation antihistamine. [21]

Research

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. [21] The results of this research indicated that bilastine was at least as efficient as cetirizine in reducing histamine-mediated effects in healthy volunteers. Notably, 20 and 50 mg of bilastine reduced the wheal and flare reaction faster than cetirizine. [21]

Related Research Articles

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.

<span class="mw-page-title-main">Diphenhydramine</span> Antihistamine medication

Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea. It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.

<span class="mw-page-title-main">Loratadine</span> Antihistamine medication

Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis and hives. It is also available in drug combinations such as loratadine/pseudoephedrine, in which it is combined with pseudoephedrine, a nasal decongestant. It is taken orally.

<span class="mw-page-title-main">Hydroxyzine</span> Antihistamine drug

Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an antihistamine medication. It is used in the treatment of itchiness, insomnia, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or injection into a muscle.

<span class="mw-page-title-main">Desloratadine</span> Allergy medication

Desloratadine (trade names Clarinex and Aerius) is a tricyclic H1 inverse agonist that is used to treat allergies. It is an active metabolite of loratadine.

<span class="mw-page-title-main">Hives</span> Skin disease characterized by red, raised, and itchy bumps

Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.

<span class="mw-page-title-main">Cetirizine</span> Antihistamine medication

Cetirizine is a second-generation antihistamine used to treat allergic rhinitis, dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within thirty minutes and last for about a day. The degree of benefit is similar to other antihistamines such as diphenhydramine, which is a first-generation antihistamine.

<span class="mw-page-title-main">Fexofenadine</span> Antihistamine medication

Fexofenadine, sold under the brand name Allegra among others, is an antihistamine pharmaceutical drug used in the treatment of allergy symptoms, such as hay fever and urticaria.

<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Levocetirizine</span> Antihistamine drug

Levocetirizine, sold under the brand name Xyzal, among others, is a second-generation antihistamine used for the treatment of allergic rhinitis and long-term hives of unclear cause. It is less sedating than older antihistamines. It is taken by mouth.

<span class="mw-page-title-main">Ketotifen</span> Antihistamine medication

Ketotifen is an antihistamine medication and a mast cell stabilizer commonly used to treat allergic conditions such as conjunctivitis, asthma, and urticaria (hives). Ketotifen is available in ophthalmic and oral forms: the ophthalmic form relieves eye itchiness and irritation associated with seasonal allergies, while the oral form helps prevent systemic conditions such as asthma attacks and allergic reactions. In addition to treating allergies, ketotifen has shown efficacy in managing systemic mast cell diseases such as mastocytosis and mast cell activation syndrome (MCAS), which involve abnormal accumulation or activation of mast cells throughout the body. Ketotifen is also used for other allergic-type conditions like atopic dermatitis (eczema) and food allergies.

<span class="mw-page-title-main">Chloropyramine</span> Chemical compound

Chloropyramine is a classical first-generation antihistamine drug approved in Eastern European countries for the treatment of allergic conjunctivitis, allergic rhinitis, bronchial asthma, and other atopic (allergic) conditions. Related indications for clinical use include angioedema, allergic reactions to insect bites, food and drug allergies, and anaphylactic shock.

<span class="mw-page-title-main">Azelastine</span> Chemical compound

Azelastine, sold under the brand name Optivar among others, is a H1 receptor-blocking medication primarily used as a nasal spray to treat allergic rhinitis (hay fever) and as eye drops for allergic conjunctivitis. Other uses may include asthma and skin rashes for which it is taken by mouth. Onset of effects is within minutes when used in the eyes and within an hour when used in the nose. Effects last for up to 12 hours.

<span class="mw-page-title-main">Acrivastine</span> Chemical compound

Acrivastine is a medication used for the treatment of allergies and hay fever. It is a second-generation H1-receptor antagonist antihistamine and works by blocking histamine H1 receptors.

<span class="mw-page-title-main">Mequitazine</span> Chemical compound

Mequitazine (trade name Primalan) is an H1 antagonist and anticholinergic of the phenothiazine chemical class. It is used to treat allergies and rhinitis.

<span class="mw-page-title-main">Ebastine</span> Chemical compound

Ebastine is a H1 antihistamine with low potential for causing drowsiness.

<span class="mw-page-title-main">Rupatadine</span> Second generation H1-antihistamine

Rupatadine is a second generation antihistamine and platelet-activating factor antagonist used to treat allergies. It was discovered and developed by Uriach and is marketed as Rupafin and under several other trade names.

<span class="mw-page-title-main">Antihistamine</span> Drug that blocks histamine or histamine agonists

Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.

<span class="mw-page-title-main">Bepotastine</span> Chemical compound

Bepotastine is a 2nd generation antihistamine. It was approved in Japan for use in the treatment of allergic rhinitis and urticaria/pruritus in July 2000, and January 2002, respectively. It is marketed in the United States as an eye drop under the brand name Bepreve, by ISTA Pharmaceuticals, a subsidiary of Bausch + Lomb.

<span class="mw-page-title-main">Ze339</span>

Ze339 brand herbal extracts are taken from the leaves of a unique variety (Petzell) of the butterbur plant. Petzell is grown on GAP-managed farms in Europe.

References

  1. 1 2 3 4 5 6 7 8 "Australian Product Information - Allertine (Bilastine) tablet". Therapeutic Goods Administration . 27 April 2022. Archived from the original on 13 September 2022. Retrieved 13 September 2022.
  2. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 21 December 2022. Archived from the original on 3 April 2022. Retrieved 2 January 2023.
  3. ↑ "Public summary - ALLERTINE bilastine 20 mg tablet blister pack". Therapeutic Goods Administration . 27 April 2022. Archived from the original on 7 December 2022. Retrieved 13 September 2022.
  4. 1 2 "Ilaxten 20 mg tablets - Summary of Product Characteristics (SmPC)". (emc). Archived from the original on 24 June 2021. Retrieved 16 June 2021.
  5. ↑ Corcóstegui R, Labeaga L, Innerárity A, Berisa A, Orjales A (2005). "Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity". Drugs in R&D. 6 (6): 371–384. doi:10.2165/00126839-200506060-00005. PMID   16274260. S2CID   23407135.
  6. 1 2 3 4 Jáuregui I, Bartra J, del Cuvillo A, Dávila I, Ferrer M, Montoro J, et al. (2011). "Bilastine and quality of life". Journal of Investigational Allergology & Clinical Immunology. 21 (Suppl 3): 16–23. PMID   22185046.
  7. ↑ Cumulative Nce introduction index, 1983–2010. Annual Reports in Medicinal Chemistry. Vol. 46. 2011. pp. 531–551. doi:10.1016/B978-0-12-386009-5.00035-7. ISBN   9780123860095.
  8. ↑ Bilastine Approval Status Archived 2023-08-27 at the Wayback Machine , drugs.com
  9. 1 2 3 Bousquet J, Ansótegui I, Canonica GW, Zuberbier T, Baena-Cagnani CE, Bachert C, et al. (January 2012). "Establishing the place in therapy of bilastine in the treatment of allergic rhinitis according to ARIA: evidence review". Current Medical Research and Opinion. 28 (1): 131–139. doi:10.1185/03007995.2011.648263. PMID   22149770. S2CID   8429174.
  10. 1 2 Bachert C, Kuna P, Sanquer F, Ivan P, Dimitrov V, Gorina MM, et al. (Bilastine International Working Group) (January 2009). "Comparison of the efficacy and safety of bilastine 20 mg vs desloratadine 5 mg in seasonal allergic rhinitis patients". Allergy. 64 (1): 158–165. doi:10.1111/j.1398-9995.2008.01813.x. PMID   19132976. S2CID   20109223.
  11. ↑ Church MK, Labeaga L (September 2017). "Bilastine: a new H1 -antihistamine with an optimal profile for updosing in urticaria". Journal of the European Academy of Dermatology and Venereology. 31 (9): 1447–1452. doi:10.1111/jdv.14305. PMID   28467671. S2CID   35712759.
  12. 1 2 3 "Allertine (bilastine)". MIMS . Archived from the original on 28 November 2023. Retrieved 13 September 2022.
  13. ↑ Horak F, Zieglmayer P, Zieglmayer R, Lemell P (May 2010). "The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber". Inflammation Research. 59 (5): 391–398. doi:10.1007/s00011-009-0117-4. PMID   19943178. S2CID   30289994.
  14. 1 2 Kuna P, Bachert C, Nowacki Z, van Cauwenberge P, Agache I, Fouquert L, et al. (Bilastine International Working Group) (September 2009). "Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo for the symptomatic treatment of seasonal allergic rhinitis: a randomized, double-blind, parallel-group study". Clinical and Experimental Allergy. 39 (9): 1338–1347. doi:10.1111/j.1365-2222.2009.03257.x. PMID   19438584. S2CID   42461412.
  15. ↑ Zuberbier T, Oanta A, Bogacka E, Medina I, Wesel F, Uhl P, et al. (April 2010). "Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled study". Allergy. 65 (4): 516–528. doi:10.1111/j.1398-9995.2009.02217.x. PMID   19860762. S2CID   24312427.
  16. 1 2 Tyl B, Kabbaj M, Azzam S, Sologuren A, Valiente R, Reinbolt E, et al. (June 2012). "Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis". Journal of Clinical Pharmacology. 52 (6): 893–903. doi:10.1177/0091270011407191. PMID   21642470. S2CID   11649589.
  17. 1 2 Graff C, Struijk JJ, Kanters JK, Andersen MP, Toft E, Tyl B (May 2012). "Effects of bilastine on T-wave morphology and the QTc interval: a randomized, double-blind, placebo-controlled, thorough QTc study". Clinical Drug Investigation. 32 (5): 339–351. doi:10.2165/11599270-000000000-00000. PMID   22393898. S2CID   22766684.
  18. ↑ Bachert C, Kuna P, Zuberbier T (1 June 2010). "Bilastine in allergic rhinoconjunctivitis and urticaria". Allergy. 65: 1–13. doi: 10.1111/j.1398-9995.2010.02404.x . S2CID   52228628.
  19. ↑ Bailey DG (November 2010). "Fruit juice inhibition of uptake transport: a new type of food-drug interaction". British Journal of Clinical Pharmacology. 70 (5): 645–655. doi:10.1111/j.1365-2125.2010.03722.x. PMC   2997304 . PMID   21039758.
  20. ↑ Corcóstegui R, Labeaga L, Innerárity A, Berisa A, Orjales A (2005). "Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity". Drugs in R&D. 6 (6): 371–384. doi:10.2165/00126839-200506060-00005. PMID   16274260. S2CID   23407135.
  21. 1 2 3 4 5 6 7 8 9 10 Jáuregui I, García-Lirio E, Soriano AM, Gamboa PM, Antépara I (January 2012). "An overview of the novel H1-antihistamine bilastine in allergic rhinitis and urticaria". Expert Review of Clinical Immunology. 8 (1): 33–41. doi:10.1586/eci.11.87. PMID   22149338. S2CID   207209051.
  22. ↑ Jauregizar N, de la Fuente L, Lucero ML, Sologuren A, Leal N, Rodríguez M (1 August 2009). "Pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effect of bilastine". Clinical Pharmacokinetics. 48 (8): 543–554. doi:10.2165/11317180-000000000-00000. PMID   19705924. S2CID   552051.
  23. ↑ Church MK (2021). "Antihistamines". Urticaria and Angioedema. Springer International Publishing. pp. 153–165. doi:10.1007/978-3-030-84574-2_11. ISBN   978-3-030-84573-5. S2CID   239944965.
  24. ↑ Montoro J, Mullol J, Dávila I, Ferrer M, Sastre J, Bartra J, et al. (2011). "Bilastine and the central nervous system". Journal of Investigational Allergology & Clinical Immunology. 21 (Suppl 3): 9–15. PMID   22185045.
  25. ↑ "Human mass balance with [14 C]-bilastine following oral administration to healthy volunteers". Basic Clin. Pharmacol. Toxicol. 105. 2009.
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