Method and system for the treatment of chronic obstructive pulmonary disease with nebulized anticholinergic administrations

Abstract

A method is provided for improving lung function in COPD by administering a muscarinic antagonist with a high efficiency nebulizer.

What is claimed is: 
     
         1 . A method of treating a patient having chronic obstructive pulmonary disease (COPD), comprising administering to the patient, with a high efficiency nebulizer, a nominal dose of a composition comprising a muscarinic antagonist that provides the patient with a therapeutic effect at least about 24 hours after administering the muscarinic antagonist to the patient. 
     
     
         2 . The method of  claim 1 , wherein the therapeutic effect 24 hours after administering the muscarinic antagonist to the patient includes an improvement in FEV 1  of at least 100 mL above baseline when adjusted for placebo or at least about 10% above baseline when adjusted for placebo. 
     
     
         3 . The method of  claim 1 , wherein the composition comprising the muscarinic antagonist contains about 25 μg to about 1000 μg of glycopyrrolate as the muscarinic antagonist. 
     
     
         4 . The method of  claim 1 , wherein the composition comprising the muscarinic antagonist contains about 25 μg to about 400 μg of glycopyrrolate as the muscarinic antagonist. 
     
     
         5 . The method of  claim 1 , wherein administering the nominal dose of the muscarinic antagonist to the patient provides an FEV 1  change from baseline area under the curve (AUC) from 12 to 24 hours after the muscarinic antagonist is administered to the patient of at least about 500 mL·hr or a magnitude of improvement of a least 4× compared to the same dose in a conventional nebulizer. 
     
     
         6 . The method of  claim 5 , wherein the muscarinic antagonist is glycopyrrolate. 
     
     
         7 . A method of treating a patient having chronic obstructive pulmonary disease (COPD), comprising administering to the patient, with a high efficiency nebulizer, a nominal dose of a composition comprising a muscarinic antagonist, wherein administering said nominal dose with said high efficiency nebulizer provides to the patient: (1) an increased magnitude and/or duration of therapeutic effect; and (2) reduced or acceptable side effects, compared to administering the same nominal dose of the muscarinic antagonist with a conventional nebulizer. 
     
     
         8 . The method of  claim 7 , wherein administering said nominal dose with the high efficiency nebulizer produces in the patient an increased duration of therapeutic effect compared to administering the same nominal dose of the muscarinic antagonist with a conventional nebulizer. 
     
     
         9 . The method of  claim 8 , wherein the composition comprising the muscarinic antagonist contains about 25 μg to about 1000 μg of glycopyrrolate as the muscarinic antagonist. 
     
     
         10 . The method of  claim 8 , wherein the composition comprising the muscarinic antagonist contains about 25 μg to about 400 μg of glycopyrrolate as the muscarinic antagonist. 
     
     
         11 . The method of  claim 8 , wherein the therapeutic effect 24 hours after administering the muscarinic antagonist to the patient includes an improvement in FEV 1  of at least 100 mL above baseline when adjusted for placebo or at least about 10% above baseline when adjusted for placebo. 
     
     
         12 . The method of  claim 7 , wherein administration of glycopyrrolate with a high efficiency nebulizer achieves an improvement in peak FEV 1  of at least about 45 mL 
     
     
         13 . A method of treating a patient having chronic obstructive pulmonary disease (COPD), comprising administering to the patient, with a nebulizer, a nominal dose of a composition comprising a muscarinic antagonist that is effective to provide the patient with a therapeutic effect for at least about 24 hours. 
     
     
         14 . The method of  claim 13 , wherein the muscarinic antagonist is glycopyrrolate. 
     
     
         15 . The method of  claim 14 , wherein the muscarinic antagonist is about 25 μg to about 1000 μg of glycopyrrolate. 
     
     
         16 . The method of  claim 13 , wherein the nebulizer is a high efficiency nebulizer. 
     
     
         17 . The method of  claim 16 , wherein the muscarinic antagonist is about 25 μg to about 400 μg of glycopyrrolate. 
     
     
         18 . A composition for administration with a high efficiency nebulizer, comprising 25 μg to about 1000 μg of glycopyrrolate in less than 1 mL in a pH optimized, preservative-free, aqueous solution. 
     
     
         19 . The composition of  claim 18 , in a dosage unit adapted for use in a high efficiency nebulizer. 
     
     
         20 . A method of treating a patient having chronic obstructive pulmonary disease (COPD), comprising administering to the patient, with a high efficiency nebulizer, a nominal dose of a composition according to  claim 18 . 
     
     
         21 . The method of  claim 20 , wherein the treatment achieves a clinically meaningful improvement in lung function for at least about 24 hours after the composition is administered. 
     
     
         22 . A method of treating a respiratory condition, comprising prolonging a duration of therapeutic effect of an inhaled active pharmaceutical ingredient by administering the active pharmaceutical ingredient with a high efficiency nebulizer. 
     
     
         23 . The method of  claim 22 , wherein the duration of therapeutic effect is at least 24 hours. 
     
     
         24 . The method of  claim 22 , wherein the active pharmaceutical ingredient is a long acting muscarinic antagonist, a short acting muscarinic antagonist, a long acting beta 2 adrenoceptor agonist, a short acting beta 2-adrenoceptor agonist, a corticosteroid, and/or a non-steroidal antiinflammatory agent. 
     
     
         25 . The method of  claim 22 , wherein the active pharmaceutical ingredient is one or more of glycopyrrolate, tiotropium, aclidinium, trospium, darotropium, QAT 370, GSK 233705, GSK 573719, GSK 656398, TD4208, BEA 218 or a pharmaceutical acceptable derivative, salt, enantiomer, diastereomer, or racemic mixture thereof. 
     
     
         26 . The method of  claim 22 , wherein the duration of therapeutic effect is at least about 24 hours and the therapeutic effect includes an improvement in FEV 1  of at least 100 mL above baseline when adjusted for placebo or at least about 10% above baseline when adjusted for placebo. 
     
     
         27 . The method of  claim 22 , wherein administering the active pharmaceutical ingredient with the high efficiency nebulizer provides a FEV 1  change above baseline area under the curve (AUC) from 12 to 24 hours after administration of the muscarinic antagonist to the patient of at least about 500 mL·h, 
     
     
         28 . A method of treating a patient having chronic obstructive pulmonary disease (COPD), comprising administering to the patient, with a high efficiency nebulizer, a composition comprising a muscarinic antagonist that provides to the patient a respirable dose or deposited dose of a muscarinic antagonist, wherein achievement of said respirable dose or deposited dose with said high efficiency nebulizer provides to the patient: (1) a similar or an increased magnitude and/or duration of therapeutic effect; and (2) reduced or acceptable side effects, compared to achievement of the same respirable dose or deposited dose of the muscarinic antagonist with a conventional nebulizer. 
     
     
         29 . The method of  claim 28 , wherein achievement of the respirable dose or deposited dose with the high efficiency nebulizer produces in the patient an increased duration of therapeutic effect of at least 24 hours after administration of the nominal dose. 
     
     
         30 . The method of  claim 28 , wherein the therapeutic effect comprises an improvement of FEV 1  of at least about 100 mL above baseline when adjusted for placebo or at least about 10% above baseline, when adjusted for placebo, 24 hours after the composition is administered with the high efficiency nebulizer. 
     
     
         31 . The method of  claim 28 , wherein administration of glycopyrrolate with a high efficiency nebulizer achieves an improvement in peak FEV 1  of at least about 45 mL. 
     
     
         32 . A method of treating a patient having chronic obstructive pulmonary disease (COPD), comprising administering to the patient, with a nebulizer, a dose of glycopyrrolate, wherein the administration produces in the patient an area under the plasma concentration curve of glycopyrrolate (AUC) of at least about 100 μg/mL·hr. 
     
     
         33 . The method of  claim 32 , wherein the administration of the dose of glycopyrrolate achieves in the patient a ratio of AUC to maximum plasma concentration of glycopyrrolate (Cmax) of at least about 0.6 hr, at least about 0.75 hr, at least about 1.0 hr, at least about 1.25 hr, or at least about 1.5 hr. 
     
     
         34 . The method of  claim 32 , wherein the method results in a therapeutic effect for at least about 24 hours after administering the glycopyrrolate. 
     
     
         35 . The method of  claim 34 , wherein the glycopyrrolate dose is about 25 μg to about 1000 μg of glycopyrrolate. 
     
     
         36 . The method of  claim 33 , wherein the glycopyrrolate dose is about 25 μg to about 400 μg of glycopyrrolate. 
     
     
         37 . The method of  claim 33 , wherein the therapeutic effect comprises an improvement of FEV 1  of at least about 100 mL above baseline when adjusted for placebo or at least about 10% above baseline when adjusted for placebo 24 hours after the glycopyrrolate is administered with the nebulizer. 
     
     
         38 . The method of  claim 33 , wherein the nebulizer is a high efficiency nebulizer.