Pharmacokinetic-Pharmacodynamic Modelling of the Antihistaminic (H1) Effect of Bilastine

  title={Pharmacokinetic-Pharmacodynamic Modelling of the Antihistaminic (H1) Effect of Bilastine},
  author={Nerea Jauregizar and Leire de la Fuente and Mar{\'i}a Luisa Lucero and Ander Sologuren and Nerea Leal and M{\'o}nica Rodr{\'i}guez},
  journal={Clinical Pharmacokinetics},
ObjectiveTo model the pharmacokinetic and pharmacodynamic relationship of bilastine, a new histamine H1 receptor antagonist, from single- and multiple-dose studies in healthy adult subjects.MethodsThe pharmacokinetic model was developed from different single-dose and multiple-dose studies. In the single-dose studies, a total of 183 subjects received oral doses of bilastine 2.5, 5, 10, 20, 50, 100, 120, 160, 200 and 220 mg. In the multiple-dose studies, 127 healthy subjects received bilastine 10… 

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

Bilastine exhibits similar single- and multiple-dose pharmacokinetic and pharmacodynamic characteristics in healthy Japanese subjects compared with those observed in Caucasian subjects in previous studies.

Evaluation of the Single-dose Pharmacokinetics of Bilastine in Subjects with Various Degrees of Renal Insufficiency

Although exposure to bilastine was higher in renally impaired subjects, it remained well within the safety margins, thus allowing the conclusion that a 20-mg daily dose can be safely administered to subjects with different degrees of renal insufficiency without the need for dose adjustments.

Safety profile of bilastine: 2nd generation H1-antihistamines.

  • F. Scaglione
  • Medicine, Biology
    European review for medical and pharmacological sciences
  • 2012
Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism, and it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

Pharmacokinetics and Safety of a Bilastine Once-Daily, Preservative-Free, Ophthalmic Formulation

The bilastine ophthalmic formulation showed a good safety profile after multiple dose administration and was well tolerated by healthy adults in an open-label, single-centre, phase I, bioavailability clinical trial.

Oral Availability of Bilastine

The absorption of bilastine after oral administration to healthy subjects was rapid, and the absolute oral bioavailability was moderate, which was in line with previous studies.

Bioequivalence Evaluation of Three Pediatric Oral Formulations of Bilastine in Healthy Subjects: Results from a Randomized, Open Label, Crossover Study

Bilastine was well tolerated when administered indistinctly as an orodispersible tablet or as an oral solution and was bioequivalent to the reference formulation.

An overview of the novel H1-antihistamine bilastine in allergic rhinitis and urticaria

Clinical studies in allergic rhinitis and chronic urticaria show that once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient’s quality of life, with at least comparable efficacy to other nonsedative H1-antihistamines.

Bilastine: a lifetime companion for the treatment of allergies

Bilastine is a suitable option for the treatment of patients with allergic rhinoconjunctivitis or urticaria across age groups from school-age children to elderly patients, and has been shown to improve health-related quality of life.

Model Informed Pediatric Development Applied to Bilastine: Ontogenic PK Model Development, Dose Selection for First Time in Children and PK Study Design

The model successfully predicted bilastine PK in pediatrics and optimally assisted the selection of the dose and sampling scheme for the trial in children.

Safety and efficacy of bilastine: a new H1-antihistamine for the treatment of allergic rhinoconjunctivitis and urticaria

  • M. Church
  • Medicine
    Expert opinion on drug safety
  • 2011
Bilastine has high selectivity for H1-receptors, is rapidly and effectively absorbed, undergoes negligible metabolism and is a substrate for P-glycoprotein, which limits its passage across the blood–brain barrier.



A pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effects of cetirizine.

The pharmacokinetic-pharmacodynamic modelling developed here characterizes the time course of cetirizine effect on histamine-induced skin reactions (wheal and flare) and shows that at this dosage the histamines-induced flare was at least 80% inhibited at the start of the second administration and the response control was nearly total.

Clinical Pharmacology of New Histamine H1 Receptor Antagonists

Most orally administered new H1 receptor antagonists are well absorbed and appear to be extensively distributed into body tissues; many are highly protein-bound.

Comparative activity of cetirizine and mizolastine on histamine-induced skin wheal and flare responses at 24 h.

This study shows that cetirizine ( 10 mg) suppresses skin reactivity to histamine more effectively than mizolastine (10 mg) 24 h after intake in healthy volunteers.

Understanding the Dose-Effect Relationship

The design of rational dosing regimens for clinical therapeutics cannot be performed with a knowledge of pharmacokinelics alone, and the linking of pharmacokinetics and pharmacodynamics to predict firstly the dose-concentration, and then the concentration-effect relationship is required.

Preclinical Pharmacology of Bilastine, a New Selective Histamine H1 Receptor Antagonist

These preclinical studies provide evidence that bilastine has H1-antihistamine activity, with high specificity for H 1-receptors, and poor or no affinity for other receptors.

In Vivo Pharmacological Characterisation of Bilastine, a Potent and Selective Histamine H1 Receptor Antagonist

In vivo preclinical studies corroborate those obtained from previously conducted in vitro experiments of bilastine, and provide evidence that bilastines possesses antihistaminic as well as antiallergic properties, with similar potency to cetirizine and superior potency to fexofenadine.

Comparison of four basic models of indirect pharmacodynamic responses

Four basic models for characterizing indirect pharmacodynamic responses after drug administration have been developed and compared and it was found that the responses produced showed a slow onset and a slow return to baseline.

Inhibition of Histamine‐Induced Skin Wheal and Flare after 5 days of Mizolastine

This study confirms that mizolastine is a rapid and potent antihistamine; and its long‐lasting effectiveness indicates that a once‐daily regimen is acceptable for clinical use.