Peak concentrations are 270 mg/mL and 308 mg/mL following a single and repeated 5 mg dose once daily, respectively. Peak plasma concentrations are achieved 0.9 h after dosing. Levocetirizine is rapidly and extensively absorbed following oral administration. The pharmacokinetics of Montelukast in patients with more severe hepatic impairment or with hepatitis has not been evaluated. No dosage adjustment is required in patients with mild to moderate hepatic insufficiency. The elimination of Montelukast was slightly prolonged compared with that in healthy subjects (mean half-life, 7.4 hours). Patients with mild to moderate hepatic insufficiency and clinical evidence of cirrhosis had evidence of decreased metabolism of Montelukast resulting in 41% (90% Cl=7%, 85%) higher mean Montelukast area under the plasma concentration curve (AUC) following a single 10 mg dose.
#ENROUTE 4 COMPARTMENT PILL BOX PLUS#
Due to the Levocetirizine component of MONTELUKAST PLUS LEVOCETIRIZINE however, dosage adjustment is required in patients with renal impairement ( See Dosage and Administration – Patients with Renal Impairment). Since Montelukast and its metabolites are not excreted in the urine, the pharamacokinetics of Montelukast was not evaluated in patients with renal insufficiency. Due to the Levocetirizine component of Montelukast plus Levocetirizine however, dosage adjustment may be required in elderly patients ( See Dosage and Administration – Elderly). The plasma half-life of Montelukast is slightly longer in the elderly. The phramcokinetic profile and the oral bioavailability of a single 10 mg oral dose of Montelukast are similar in elderly and younger adults. Coupled with estimates of Montelukast oral bioavailability, this indicates than Montelukast and its metabolites are excreted almost exclusively via the bile. Following an oral dose of radio labeled Montelukast, 86% of the radioactivity was recovered in 5-day fecal collections and 0.2% was recovered in urine. The plasma clearance of Montelukast averages 45 mL/min in healthy adults. The contribution of metabolites to the therapeutic effect of Montelukast is minimal. In vitro studies using human liver microsomes indicate that cytochrome P450 3A4, 2A6 and 2C9 are involved in the metabolism of Montelukast.īased on further in vitro results in human liver microsomes, therapeutic plasma concentrations of Montelukast do not inhibit cytochrome P450 3A4, 2C9 1A2, 2A6, 2C10 or 2D6. In studies with therapeutic doses, plasma concentrations of metabolites of Montelukast are undetected at steady state in adults and children. In addition, concentrations of radio labeled material at 234 hours post dose were minimal in all other tissues. Studies in rats with radio labeled Montelukast indicate minimal distribution across the blood-brain barrier. Steady state volume of distribution of Montelukast averages 8-11 liters. Montelukast is more than 99% bound to plasma proteins. The mean oral bioavailability is 73% and is decreased to 63% by a standard meal. C max is achieved in 2 hours after administration of the 5 mg chewable tablet in adults in the fasted state.
Safety and efficacy were demonstrated in clinical trials where the 10 mg film-coated tablet was administered without regard to the timing of food ingestion.
The oral bioavailability and (C max) are not influenced by a standard meal. Mean peak plasma concentration (C max) is achieved 3 hours (T max) after administration of a 10 mg dose in adults in the fasted state. Montelukast is rapidly absorbed following oral administration. The antihistamine activity of Levocetirizine has been documented in a variety of animal and human models. Its principal effects are mediated via selective inhibition of H 1 receptors. Levocetirizinem the active enantiomer of cetirizine, is an antihistamine. Montelukast is an orally active compound which binds with high affinity and selectively to the cysteinyl leukotriene type 1 receptor thereby preventing cysteinyl leukotriene from exerting their effects. Intranasal challenge with cysteinyl leukotrienes has been shown to increase nasal airway resistance and symptoms of nasal obstruction. In allergic rhinitis, cysteinyl leukotrienes are released from nasal mucosa after allergen exposure during both early- and late-phase reactions and are associated with symptoms of allergic rhinitis. In asthma, leukotriene mediated effects include bronchoconstriction, mucuos secretion, vascular permeability and eosinophil recruitment.
Cysteinyl leukotriene have been correlated with the pathphysiology of asthma and allergic rhinitis. These important mediators bind to cysteinyl leukotriene receptors. The cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory eicosanoids released from various cells including mast cells and eosinophils.
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