, Volume 28, Issue 5, pp 419-432
Date: 04 Nov 2012

Pharmacokinetic-Pharmacodynamic Relationships of H1-Antihistamines

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Histamine H1-receptor antagonists are reversible, competitive inhibitors of the actions of histamine, a critical mediator in the pathophysiology of the allergic response. This review is mainly devoted to second generation antihistamines that possess a low sedation potential compared with first generation compounds. The pharmacokinetic and pharmacodynamic data of 10 compounds have been updated. Some values are lacking for drugs under development, but also for older antihistamines. Thereafter, pharmacokinetic-pharmacodynamic relationships are reported from published or original documents.

A linear pharmacokinetic-pharmacodynamic relationship has been found for acrivastine, astemizole, cetirizine, ebastine and terfenadine, whereas nonlinear relationships have been calculated for ebastine (in the dog), levocabastine, mizolastine, noberastine and terfenadine. It must be concluded that this type of approach for therapeutic optimisation is very fruitful and may enable large numbers of clinical studies to be avoided.

Trends for the future include: (i) in vitro binding studies with the human H1-receptor obtained by molecular biology; (ii) the characterisation of the cytochromes P450 responsible for the biotransformation of antihistamines; (iii) the calculation of the pharmacokinetic-pharmacodynamic relationship in healthy individuals; and (iv) prospective effect-controlled clinical studies.