Levocetirizine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Levocetirizine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Levocetirizine, the active enantiomer of cetirizine, is an antihistamine; its principal effects are mediated via selective inhibition of H 1 receptors. The antihistaminic activity of levocetirizine has been documented in a variety of animal and human models. In vitro binding studies revealed that levocetirizine has an affinity for the human H 1 -receptor 2-fold higher than that of cetirizine (Ki = 3 nmol/L vs. 6 nmol/L, respectively). The clinical relevance of this finding is unknown.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Levocetirizine, the active enantiomer of cetirizine, is an antihistamine; its principal effects are mediated via selective inhibition of H 1 receptors.
The antihistaminic activity of levocetirizine has been documented in a variety of animal and human models.
In vitro binding studies revealed that levocetirizine has an affinity for the human H 1 -receptor 2-fold higher than that of cetirizine (Ki = 3 nmol/L vs.
6 nmol/L, respectively).
The clinical relevance of this finding is unknown.
12.2 Pharmacodynamics Studies in adult healthy subjects showed that levocetirizine at doses of 2.5 mg and 5 mg inhibited the skin wheal and flare caused by the intradermal injection of histamine.
In contrast, dextrocetirizine exhibited no clear change in the inhibition of the wheal and flare reaction.
Levocetirizine at a dose of 5 mg inhibited the wheal and flare caused by intradermal injection of histamine in 14 pediatric subjects (aged 6 to 11 years) and the activity persisted for at least 24 hours.
The clinical relevance of histamine wheal skin testing is unknown.
A QT/QTc study using a single dose of 30 mg of levocetirizine did not demonstrate an effect on the QTc interval.
While a single dose of levocetirizine had no effect, the effects of levocetirizine may not be at steady state following single dose.
The effect of levocetirizine on the QTc interval following multiple dose administration is unknown.
Levocetirizine is not expected to have QT/QTc effects because of the results of QTc studies with cetirizine and the long postmarketing history of cetirizine without reports of QT prolongation.
12.3 Pharmacokinetics Levocetirizine exhibited linear pharmacokinetics over the therapeutic dose range in adult healthy subjects.
Absorption Levocetirizine is rapidly and extensively absorbed following oral administration.
In adults, peak plasma concentrations are achieved 0.9 hour after administration of the oral tablet.
The accumulation ratio following daily oral administration is 1.12 with steady state achieved after 2 days.
Peak concentrations are typically 270 ng/mL and 308 ng/mL following a single and a repeated 5 mg once daily dose, respectively.
Food had no effect on the extent of exposure (AUC) of the levocetirizine tablet, but T max was delayed by about 1.25 hours and C max was decreased by about 36% after administration with a high fat meal; therefore, levocetirizine can be administered with or without food.
A dose of 5 mg (10 mL) of levocetirizine dihydrochloride oral solution is bioequivalent to a 5 mg dose of levocetirizine dihydrochloride tablets.
Pharmacokinetics
12.3 Pharmacokinetics Levocetirizine exhibited linear pharmacokinetics over the therapeutic dose range in adult healthy subjects. Absorption Levocetirizine is rapidly and extensively absorbed following oral administration. In adults, peak plasma concentrations are achieved 0.9 hour after administration of the oral tablet. The accumulation ratio following daily oral administration is 1.12 with steady state achieved after 2 days. Peak concentrations are typically 270 ng/mL and 308 ng/mL following a single and a repeated 5 mg once daily dose, respectively. Food had no effect on the extent of exposure (AUC) of the levocetirizine tablet, but T max was delayed by about 1.25 hours and C max was decreased by about 36% after administration with a high fat meal; therefore, levocetirizine can be administered with or without food. A dose of 5 mg (10 mL) of levocetirizine dihydrochloride oral solution is bioequivalent to a 5 mg dose of levocetirizine dihydrochloride tablets. Following oral administration of a 5 mg dose of levocetirizine dihydrochloride oral solution to healthy adult subjects, the mean peak plasma concentrations were achieved approximately 0.5 hour post dose. Distribution The mean plasma protein binding of levocetirizine in vitro ranged from 91 to 92%, independent of concentration in the range of 90 ng/mL to 5,000 ng/mL, which includes the therapeutic plasma levels observed. Following oral dosing, the average apparent volume of distribution is approximately 0.4 L/kg, repre