Cetirizine poorly and slowly crosses the blood-brain barrier, which is thought to be due to its chemical properties and its activity as a P-glycoprotein substrate. Metabolism
Cetirizine does not undergo extensive metabolism. It is notably not metabolized by the cytochrome P450 system. Because of this, it does not interact significantly with drugs that inhibit or induce cytochrome P450 enzymes such as theophylline, erythromycin, clarithromycin, cimetidine, or alcohol. While cetirizine does not undergo extensive metabolism or metabolism by the cytochrome P450 enzyme, it does undergo some metabolism by other means, the metabolic pathways of which include oxidation and conjugation. Plasma radioactivity attributed to unchanged cetirizine is more than 90% at 2 hours, 80% at 10 hours, and 70% at 24 hours, indicating limited and slow metabolism. The enzymes responsible for transformation of cetirizine have not been identified. Elimination
Cetirizine is eliminated approximately 70 to 85% in the urine and 10 to 13% in the feces. About 50 or 60% of cetirizine eliminated in the urine is unchanged. It is eliminated in the urine via an active transport mechanism. The elimination half-life of cetirizine ranges from 6.5 to 10 hours in healthy adults, with a mean across studies of approximately 8.3 hours. Its duration of action is at least 24 hours. The elimination half-life of cetirizine is increased in the elderly (to 12 hours), in hepatic impairment (to 14 hours), and in renal impairment (to 20 hours). Chemistry
Cetirizine contains L- and D-stereoisomers. Chemically, levocetirizine is the active L-enantiomer of cetirizine.
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.