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Pharmacotherapeutic group: Montelukast sodium is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene (CysLT 1), receptor, Levocetirizine is the R-enantiomer of cetirizine. Levocetirizine is an orally active, potent, selective and long acting H1 histamine receptor antagonist with no anticholinergic activity.
Pharmacology: Pharmacodynamics: Montelukast causes inhibition of airway cysteinyl leukotriene receptors as demonstrated by the ability to inhibit bronchoconstriction due to inhaled LTD 4 in asthmatics. Doses as low as 5 mg cause substantial blockage of LTD 4 induced bronchoconstriction. Antihistamine for systemic use, piperazine derivative, Levocetirizine, the (R) enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1 receptors. Binding studies revealed that levocetirizine has an affinity 2-fold higher than that of cetirizine. Levocetirizine dissociates from H1 receptors with half-life of 115 A,A≠38 min.
Pharmacodynamics studies in healthy volunteers demonstrate that, at half the dose, levocetirizine has comparable activity to cetirizine, both in the skin and in the nose.
Pharmacokinetics: Absorption: In combination administration of the 10 mg film-coated tablet to fasted adults, the mean peak montelukast.
Plasma concentration (Cmax) is achieved in 3 to 4 hours (Tmax). The mean oral biovailability is 64%. The oral bioavailability and Cmax are not influenced by a standard meal in the morning. Levocetirizine is rapidly and extensively absorbed following oral administration. Peak plasma concentrations are achieved 0.9 g h after dosing. Steady state is achieved after two days. Peak concentrations are typically 270 mg/mL and 308 mg/mL following a single and a repeated 5 mg o.d. dose, respectively.
The extent of absorption is dose-independent and is not altered by food, but the peak concentration is reduced and delayed.
Distribution: Montelukast and levocetirizine is more than 90%-99% bound proteins. The steady-state volume of distribution of montelukast averages 8 to 11 liters and it bounds to plasma proteins. The distribution of is restrictive, as the volume of distribution is 0.41/kg.
Metabolism: the extent of metabolism of Montelukast and levocetirizine is less than 14% of the dose and therefore differences resulting from genetic polymorphism or concomitant intake of enzyme inhibitors are expected to be negligible. Metabolic pathways include aromatic oxidation, N- and O-dealkylation and taurine conjugation. Dealkylation pathways are primarily mediated by CYP 3A4 while aromatic oxidation involved multiple and/or unidentified CYP isoforms. In combination had no effect on the activities of CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 at concentrations well above peak concentrations achieved following a 5 mg oral dose. Due to its low metabolism and absence of metabolic inhibition potential, the interaction of Montelukast and levocetirizine with other substances, or vice versa, is unlikely.
Elimination: Excretion via faeces accounts for only 12.9% of the dose. Montelukast and levocetirizine is excreted both by glomerular filtration and active tubular secretion.
