The choice of an H₁‐antihistamine for the 21st century

Summary It is clear that as a starting point an H 1 ‐antihistamine for the 21st century should be effective, but non‐sedative and non‐cardiotoxic. In addition it is desirable that an oral H 1 ‐antihistamine should be rapidly absorbed so that it can be distributed to the target organ sites, be readily bioavailable, and have a half‐life sufficient to enable once daily dosing and to have clinical effect throughout a 24‐h dosing interval. The effect of the drug should be maintained with repeated dosing. To give confidence in drug administration it should require no dosage adjustment in renally or hepatically impaired individuals and have no significant drug interactions, especially in view of past experience with drugs such as ketoconazole and macrolide antibiotics that may modify hepatic metabolism. In addition to these considerations there is a desire for a designer molecule that has activity over and beyond H 1 ‐receptor blockade, thus providing an oral therapy with a broader ‘anti‐inflammatory’ activity. Such activity may underlie the improved benefit in quality of life that is evident with some antihistamines over others. As we enter the 21st century there are a number of oral H 1 ‐antihistamines that fulfil the majority of these requirements, with fexofenadine, out of those most widely used, appearing to come closest to the desired profile.