The oral bioavailability of cetirizine is at least 70% and of levocetirizine is at least 85%. The Tmax of cetirizine is approximately 1.0 hour regardless of formulation. The pharmacokinetics of cetirizine have been found to increase linearly with dose across a range of 5 to 60 mg. Its Cmax following a single dose has been found to be 257 ng/mL for 10 mg and 580 ng/mL for 20 mg. Food has no effect on the bioavailability of cetirizine but has been found to delay the Tmax by 1.7 hours (i.e., to approximately 2.7 hours) and to decrease the Cmax by 23%. Similar findings were reported for levocetirizine, which had its Tmax delayed by 1.25 hours and its Cmax decreased by about 36% when administered with a high-fat meal. Steady-state levels of cetirizine occur within 3 days and there is no accumulation of the drug with chronic administration. Following once-daily administration of 10 mg cetirizine for ten days, the mean Cmax was 311 ng/mL. Distribution
The mean plasma protein binding of cetirizine has been found to be 93 to 96% across a range of 25 to 1,000 ng/mL independent of concentration. Plasma protein binding of 88 to 96% has also been reported across multiple studies. The drug is bound to albumin with high affinity, while α1-acid glycoprotein and lipoproteins contribute much less to total plasma protein binding. The unbound or free fraction of levocetirizine has been reported to be 8%. The true volume of distribution of cetirizine is unknown but is estimated to be 0.3 to 0.45 L/kg.
In the UK, up to 30 tablets of 10 mg are on the general sales list (of pharmaceuticals) and can be purchased without a prescription and without pharmacist supervision. The drug can be in the form of tablets, capsules or a syrup. Adverse effects
Commonly reported side effects of cetirizine include headache, dry mouth, drowsiness, and fatigue, while more serious but rare adverse effects reported include tachycardia and edema.Discontinuing cetirizine after prolonged use (typically, use beyond six months) may result in generalized itching. Pharmacology
Pharmacodynamics
Cetirizine acts as a highly selective antagonist of the histamine H1 receptor. The Ki values for the H1 receptor are approximately 6 nM for cetirizine, 3 nM for levocetirizine, and 100 nM for dextrocetirizine, indicating that the levorotatory enantiomer is the main active form. Cetirizine has 600-fold or greater selectivity for the H1 receptor over a wide variety of other sites, including muscarinic acetylcholine, serotonin, dopamine, and α-adrenergic receptors, among many others. The drug shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit anticholinergic effects. It shows negligible inhibition of the hERG channel (IC50 > 30 μM) and no cardiotoxicity has been observed with cetirizine at doses of up to 60 mg/day, six times the normal recommended dose and the highest dose of cetirizine that has been studied in healthy subjects.Cetirizine crosses the blood-brain barrier only slightly, and for this reason, produces minimal sedation compared to many other antihistamines.