The comparative pharmacokinetics of H1-receptor antagonists

H1-receptor antagonists appear to be absorbed rapidly after oral administration, with peak serum concentrations being reached one to three hours after a dose. For most of these drugs, the absolute bioavailability is unknown because no intravenous formulations are available for comparative purposes. The serum elimination half-life values of these agents are variable: a few hours for terfenadine and triprolidine; about 9 hours for cetirizine, azatadine, and loratadine; from 20 to 25 hours for hydroxyzine, chlorpheniramine, and brompheniramine; and from 5 to 14 days for astemizole. Few pharmacokinetic studies of H1-receptor antagonists in children have been reported. However, it is known that chlorpheniramine, hydroxyzine, cetirizine, and terfenadine have shorter elimination half-life values in children than in adults. Regardless of the age of patients, for most of the H1-receptor antagonists the apparent volumes of distribution and total body clearances appear to be large (3.4 to 18.5 L/kg and 4.4 to 32.1 mL/min/kg, respectively). Cetirizine is an exception, with values of 0.8 L/kg and 0.5 mL/min/kg. Urinary excretion of unchanged antihistamine is higher after cetirizine (60% of dose) than any other H1 blocker. For H1-receptor antagonists with long half-life values, steady state may not be reached for several days (chlorpheniramine and brompheniramine) or several weeks (astemizole), and significant accumulation of drug occurs if the dosing interval is more frequent than every half-life. There is no evidence for the introduction of metabolism of H1-receptor antagonists, even after months of treatment.