Pharmacodynamics<unk>  Site Ki (nM) Species Ref 5-HT2A 170 () Rat 5-HT2C α1 460 () Rat D1 >10,000 Mouse D2 378560 () MouseRat H1 2.0–196.4100 () HumanBovineRat H2 H3 H4 >10,000 Human 4,60010,00010,000 ()6,310 (pA2)3,800 HumanMouseRatGuinea pigBovine ≥3,400 () Rat Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.<unk> 's predominant mechanism of action is as a potent and selective histamine H1 receptor inverse agonist. This action is responsible for its antihistamine and sedative effects. Unlike many other first-generation antihistamines,<unk>  has a lower affinity for the muscarinic acetylcholine receptors, and in accordance, has a lower risk of anticholinergic side effects. In addition to its antihistamine activity,<unk>  has also been shown to act more weakly as an antagonist of the serotonin 5-HT2A receptor, the dopamine D2 receptor, and the α1-adrenergic receptor. The weak antiserotonergic effects of<unk>  likely underlie its usefulness as an anxiolytic, as other antihistamines without such properties have not been found to be effective in the treatment of anxiety.<unk>  crosses the blood–brain barrier easily and exerts effects in the central nervous system. A positron emission tomography (PET) study found that brain occupancy of the H1 receptor was 67.6% for a single 30 mg dose of<unk> . In addition, subjective sleepiness correlated well with the brain H1 receptor occupancy. PET studies with antihistamines have found that brain H1 receptor occupancy of more than 50% is associated with a high prevalence of somnolence and cognitive decline, whereas brain H1 receptor occupancy of less than 20% is considered to be non-sedative. Pharmacokinetics<unk>  can be administered orally or via intramuscular injection. When given orally,<unk>  is rapidly absorbed from the gastrointestinal tract. The effect of<unk>  is notable in 30 minutes.<unk>  is rapidly absorbed and distributed with oral and intramuscular administration, and is metabolized in the liver; the main metabolite (45%), cetirizine, is formed through oxidation of the alcohol moiety to a carboxylic acid by alcohol dehydrogenase, and overall effects are observed within one hour of administration. Higher concentrations are found in the skin than in the plasma. Cetirizine, although less sedating, is non-dialyzable and possesses similar antihistamine properties. The other metabolites identified include a N-dealkylated metabolite, and an O-dealkylated 1/16 metabolite with a plasma half-life of 59 hours. These pathways are mediated principally by CYP3A4 and CYP3A5. "In animals,<unk>  and its metabolites are excreted in feces via biliary elimination." The Tmax of<unk>  is about 2.0 hours in both adults and children and its elimination half-life is around 20.0 hours in adults (mean age 29.3 years) and 7.1 hours in children. Its elimination half-life is shorter in children compared to adults. In another study, the elimination half-life of<unk>  in elderly adults was 29.3 hours. One study found that the elimination half-life of<unk>  in adults was as short as 3 hours, but this may have just been due to methodological limitations. Although<unk>  has a long elimination half-life and produces antihistamine for as long as 24 hours, the CNS effects of<unk>  and other antihistamines with long half-lives seem to diminish after 8 hours. Administration in geriatrics differs from the administration of<unk>  in younger patients; according to the FDA, there have not been significant studies made (2004), which include population groups over 65, which provide a distinction between elderly aged patients and other younger groups.<unk>  should be administered carefully in the elderly with consideration given to possible reduced elimination.
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