First-generation antihistamines are well absorbed after oral administration, with peak blood levels occurring within 1 to 2 hours; the therapeutic effect usually lasts 4 to 6 hours, although some drugs are much longer acting (Table 38.2). These antagonists are generally metabolized in the liver through hydroxylation. The metabolites and a small amount of parent compound are excreted in the urine.
The second-generation Hj-receptor antagonists are also rapidly absorbed, with peak plasma concentrations being reached within 1 to 3 hours. Their duration of action generally varies between 4 and 24 hours (Table 38.2). Loratadine (Claritin) and its active metabolite, desloratadine (Clarinex), undergoes extensive first-pass metabolism and is converted by CYP3A4 isozymes to an active metabolite. A number of drug interactions result from the ability of various compounds to induce, inhibit, or compete for metabolism by this cytochrome P450 system. In contrast, cetirizine (Zyrtec) and fexofenadine (Allegra) undergo little hepatic metabolism and are eliminated mainly as unchanged compounds in the urine and feces, respectively.
The reduction in therapeutic effectiveness that can occur when antihistamines are given for long periods is probably related to an induction of hepatic drug-metabolizing enzymes. Children tend to eliminate anti-histamines more rapidly than adults, while individuals with hepatic impairment may eliminate them more slowly.
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