Pharmacokinetics of Montelukast in Asthmatic Patients 6 to 24 Months Old

Migoya, Elizabeth; Kearns, Gregory L.; Hartford, Alan; Zhao, Jamie J.; Adelsberg, Janet van; Tozzi, Carol A.; Knorr, Barbara; Deutsch, Paul

doi:10.1177/0091270004264970

Cited by 40 publications

(66 citation statements)

References 29 publications

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“…Since the inhibition of P2Y 1 receptor-elicited effects occurred without affecting specific nucleotide binding, if there is a direct interaction, it may be allosteric. The implications of these data for the clinical use of leukotriene antagonists is yet to be explored, with the question if some of their effects at therapeutic doses [44] may be related to their ability to inhibit the signaling pathways of P2Y receptors for extracellular nucleotides. These observations should foster the study of possible implications for the clinical use of these compounds in asthma or in other inflammatory conditions.…”

Section: Discussionmentioning

confidence: 99%

CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors

Mamedova

Capra

Accomazzo

et al. 2005

Biochemical Pharmacology

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Montelukast and pranlukast are orally active leukotriene receptor antagonists selective for the CysLT 1 receptor. Conversely, the hP2Y 1,2,4,6,11,12,13,14 receptors represent a large family of GPCRs responding to either adenine or uracil nucleotides, or to sugar-nucleotides. Montelukast and pranlukast were found to inhibit nucleotide-induced calcium mobilization in a human monocyte-macrophage like cell line, DMSO-differentiated U937 (dU937). Montelukast and pranlukast inhibited the effects of UTP with IC 50 values of 7.7 and 4.3 μM, respectively, and inhibited the effects of UDP with IC 50 values of 4.5 and 1.6 μM, respectively, in an insurmountable manner. Furthermore, ligand binding studies using [ 3 H]LTD 4 excluded the possibility of orthosteric nucleotide binding to the CysLT 1 receptor. dU937 cells were shown to express P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 13 and P2Y 14 receptors. Therefore, these antagonists were studied functionally in a heterologous expression system for the human P2Y receptors. In 1321N1 astrocytoma cells stably expressing human P2Y 1,2,4,6 receptors, CysLT 1 antagonists inhibited both the P2Y agonist-induced activation of phospholipase C and intracellular Ca 2+ mobilization. IC 50 values at P2Y 1 and P2Y 6 receptors were <1 μM. In control astrocytoma cells expressing an endogenous M3 muscarinic receptor, 10 μM montelukast had no effect on the carbachol-induced rise in intracellular Ca 2+ . These data demonstrated that CysLT 1 receptor antagonists interact functionally with signaling pathways of P2Y receptors, and this should foster the study of possible implications for the clinical use of these compounds in asthma or in other inflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors

Mamedova

Capra

Accomazzo

et al. 2005

Biochemical Pharmacology

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“…32 A study indicated that a single dose of montelukast (4 mg oral granules) administered to children 3-6 months of age 33 yielded systemic exposures similar to those observed in children aged 6-24 months. 34 The respective maximum plasma concentrations were 561.1 ng/ml and 514.4 ng/ml. 33,34 The pharmacokinetic profile of the 6-24 month group on a single 4 mg dose of montelukast oral granules was also compared to that of adults on 10 mg FCT.…”

Section: Plasma Concentrations In Adults and Childrenmentioning

confidence: 92%

“…34 The respective maximum plasma concentrations were 561.1 ng/ml and 514.4 ng/ml. 33,34 The pharmacokinetic profile of the 6-24 month group on a single 4 mg dose of montelukast oral granules was also compared to that of adults on 10 mg FCT. The AUCpop values were relatively similar in the two groups, while the Cmax values were 279 ng/ml and 514.4 ng/ml in adults and children respectively.…”

Section: Plasma Concentrations In Adults and Childrenmentioning

confidence: 92%

“…The AUCpop values were relatively similar in the two groups, while the Cmax values were 279 ng/ml and 514.4 ng/ml in adults and children respectively. 34 Yet another study indicated that a 5 mg chewable tablet administered once daily to children aged 6-14 years with asthma, resulted in a pharmacokinetic profile comparable to that of the clinically effective 10 mg FCT dose in adults. 35 …”

Section: Plasma Concentrations In Adults and Childrenmentioning

confidence: 99%

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Montelukast Sodium: Administration to Children to Control Intermittent Asthma

2010

Clinical Medicine Reviews in Therapeutics

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The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the chemotherapy of exercise-induced asthma. It has also been used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma because most exacerbations of this condition involve respiratory virus infection-triggered inflammatory mechanisms which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this review is to evaluate the role of montelukast in the treatment of intermittent asthma in children.

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“…Determination of the optimum daily dose of 5 mg in children aged 6-14 years [46] and 4 mg in infants as young as 6 months of age [47,203] is based on serum blood levels of the drug. For adults over 14 years of age, montelukast is provided as beige, rounded-square (7.9 × 7.9 mm), film-coated tablets, engraved 'SINGULAIR' on one side and MSD 117 on the other.…”

Section: Available and Recommended Dosingmentioning

confidence: 99%