Zyller Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Levocetirizine, an active R-enantiomer of cetirizine, is a second generation antihistamine. The drug, as other antihistamines, is reversible, competitive H₁ receptor antagonist. In in vitro binding studies, levocetirizine has a twofold higher affinity for H₁ receptor than cetirizine. Levocetirizine at a half dosage of cetirizine appears to be as potent as cetirizine in histamine-induced allergic sneezing, increased airway resistance, and skin wheal and flare.
Pharmacokinetics:Absorption: Levocetirizine is rapidly and extensively absorbed following oral administration. Peak plasma concentration (C_max) were observed at 0.9 hours and 0.5 hours after administration of levocetirizine tablets and oral solution, respectively. Coadministration of levocetirizine and high fat diet delays the absorption of levocetirizine by 1.25 hours and reduces the peak plasma concentration by approximately 36%. Area under the plasma concentration-time curve (AUC) of levocetirizine is not affected by food. Onset of action of levocetirizine occurs within 1 hour following administration on an empty stomach. Symptomatic improvement of allergic rhinitis or chronic urticaria were observed as early as 1 day after initiation of levocetirizine therapy.
Distribution: Levocetirizine distributes in total body water and expected to distribute into breast milk. The average apparent volume of distribution (V_d) of levocetirizine in human body is 0.4 L/kg and its protein binding is approximately 91-92%.
No tissue distribution data are available in humans, neither concerning the passage of levocetirizine through the blood-brain-barrier.
Metabolism and Elimination: A small amount of levocetirizine (less than 14% of administered dose) is metabolized by hepatic enzyme systems including aromatic oxidation, N-dealkylation, O-dealkylation, and taurine conjugation. 85.4% of the dose is excreted in urine via glomerular filtration and active tubular secretion. 12.9% of the dose is found in feces. The half-life (T_1/2) of levocetirizine in healthy adult is approximately 8-9 hours. In patients with renal impairment, the elimination half-life is increased by 1.4-, 2-, 2.9-, or 4-fold in those with mild, moderate, severe impairment, or end-stage renal impairment, respectively.