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

@article{Jauregizar2009PharmacokineticPharmacodynamicM,
  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},
  year={2009},
  volume={48},
  pages={543-554}
}
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… 

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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.

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

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References

SHOWING 1-10 OF 21 REFERENCES

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.