|
|
|||
|
|||
|
|
|||
|
food allergy network |
|||
|
|
|||
|
|||
 
|
|||
|
|
|||
|
food allergy network DESCRIPTION Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist(LTRA), with the chemical name 4-(5-cyclopentyloxy-carbonylamino-1-methyl-indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide food allergy network. The molecular weight of zafirlukast is 575.7 and the structural formula is:
Zafirlukast, a fine white to pale yellow amorphous powder, is practically insolublein water food allergy network. It is slightly soluble in methanol and freely soluble in tetrahydrofuran,dimethylsulfoxide, and acetone food allergy network. ACCOLATE is supplied as 10 and 20 mg tablets for oral administration food allergy network. Inactive Ingredients: Film-coated tablets containing croscarmellose sodium,lactose, magnesium stearate, microcrystalline cellulose, povidone, hypromellose,and titanium dioxide food allergy network.
In vitro studies demonstrated that zafirlukast antagonized the contractileactivity of three leukotrienes (LTC 4 , LTD 4 and LTE 4 ) in conducting airwaysmooth muscle from laboratory animals and humans food allergy network. Zafirlukast prevented intradermalLTD 4 -induced increases in cutaneous vascular permeability and inhibited inhaledLTD 4 -induced influx of eosinophils into animal lungs food allergy network. Inhalational challengestudies in sensitized sheep showed that zafirlukast suppressed the airway responsesto antigen; this included both the early- and late-phase response and the nonspecifichyperresponsiveness food allergy network. In humans, zafirlukast inhibited bronchoconstriction caused by several kindsof inhalational challenges food allergy network. Pretreatment with single oral doses of zafirlukastinhibited the bronchoconstriction caused by sulfur dioxide and cold air in patientswith asthma food allergy network. Pretreatment with single doses of zafirlukast attenuated the early-and late-phase reaction caused by inhalation of various antigens such as grass,cat dander, ragweed, and mixed antigens in patients with asthma food allergy network. Zafirlukastalso attenuated the increase in bronchial hyperresponsiveness to inhaled histaminethat followed inhaled allergen challenge food allergy network. Clinical Pharmacokinetics and Bioavailability: Distribution Metabolism Excretion In the pivotal bioequivalence study, the mean terminal half-life of zafirlukastis approximately 10 hours in both normal adult subjects and patients with asthma food allergy network. In other studies, the mean plasma half-life of zafirlukast ranged from approximately8 to 16 hours in both normal subjects and patients with asthma food allergy network. The pharmacokineticsof zafirlukast are approximately linear over the range from 5 mg to 80 mg food allergy network. Steady-stateplasma concentrations of zafirlukast are proportional to the dose and predictablefrom single-dose pharmacokinetic data food allergy network. Accumulation of zafirlukast in the plasmafollowing twice-daily dosing is approximately 45% food allergy network. The pharmacokinetic parameters of zafirlukast 20 mg administered as a singledose to 36 male volunteers are shown with the table below food allergy network. Mean (% Coefficient of Variation) pharmacokinetic
Race: No differences in the pharmacokinetics of zafirlukast due to race havebeen observed food allergy network. Elderly: The apparent oral clearance of zafirlukast decreases with age food allergy network. Inpatients above 65 years of age, there is an approximately 2-3 fold greater Cmax and AUC compared to young adult patients food allergy network. Children: Following administration of a single 20 mg dose of zafirlukast to20 boys and girls between 7 and 11 years of age, and in a second study, to 29boys and girls between 5 and 6 years of age, the following pharmacokinetic parameterswere obtained: Parameter Children age
Zafirlukast disposition was unchanged after multiple dosing (20 mg twice daily)in children and the degree of accumulation in plasma was similar to that observedin adults food allergy network. Hepatic Insufficiency: In a study of patients with hepatic impairment (biopsy-provencirrhosis), there was a reduced clearance of zafirlukast resulting in a 50-60%greater C max and AUC compared to normal subjects food allergy network. Renal Insufficiency: Based on a cross-study comparison, there are no apparentdifferences in the pharmacokinetics of zafirlukast between renally-impairedpatients and normal subjects food allergy network. Drug-Drug Interactions
|
|||
 
|
|||
|
|
|||
|
|
|||
|
|
|||
|
|
|||
|
|
|||
| ffood allergy network foood allergy network foood allergy network foodd allergy network food allergy network food aallergy network food alllergy network food alllergy network food alleergy network food allerrgy network food allerggy network food allergyy network food allergy network food allergy nnetwork food allergy neetwork food allergy nettwork food allergy netwwork food allergy netwoork food allergy networrk food allergy networkk ood allergy network fod allergy network fod allergy network foo allergy network foodallergy network food llergy network food alergy network food alergy network food allrgy network food allegy network food allery network food allerg network food allergynetwork food allergy etwork food allergy ntwork food allergy nework food allergy netork food allergy netwrk food allergy netwok food allergy networ f ood allergy network fo od allergy network foo d allergy network food allergy network food allergy network food a llergy network food al lergy network food all ergy network food alle rgy network food aller gy network food allerg y network food allergy network food allergy network food allergy n etwork food allergy ne twork food allergy net work food allergy netw ork food allergy netwo rk food allergy networ k food allergy network ofod allergy network food allergy network fodo allergy network foo dallergy network fooda llergy network food lalergy network food allergy network food alelrgy network food allregy network food allegry network food alleryg network food allerg ynetwork food allergyn etwork food allergy entwork food allergy ntework food allergy newtork food allergy netowrk food allergy netwrok food allergy netwokr afood allergy network thefood allergy network food allergy network | |||
|
|
|||
|
|
|||
|
|
|||
|
Copyright 2005 D-S LTD. |
