Use of a celecoxib composition for fast pain relief

Abstract

There is provided a method of rapidly relieving pain in a mammalian, preferably human, subject. The method comprises orally administering to the subject an effective pain-relieving amount of a composition comprising celecoxib formulated in such a way as to provide, when tested in fasting humans in accordance with standard pharmacokinetic practice, a blood plasma concentration profile of celecoxib in which a concentration of about 250 ng/ml is attained not later than about 30 minutes after oral administration.

What is claimed is:  
     
         1 . A therapeutic method comprising orally administering to a mammalian subject in need of analgesia an effective pain-relieving amount of a composition comprising celecoxib formulated in such a way as to provide, when tested in fasting humans in accordance with standard pharmacokinetic practice, a blood plasma concentration profile of celecoxib in which a concentration of at least about 250 ng/ml is attained not later than about 30 minutes after oral administration.  
     
     
         2 . The method of  claim 1  wherein the composition is administered in an amount providing about 50 to about 400 mg celecoxib.  
     
     
         3 . The method of  claim 2  wherein the composition is administered in an amount providing about 100 to about 275 mg celecoxib.  
     
     
         4 . The method of  claim 1  wherein the mammalian subject is a human subject.  
     
     
         5 . The method of  claim 1  wherein a plasma concentration of celecoxib of at least about 300 ng/ml is attained not later than about 30 minutes after oral administration.  
     
     
         6 . The method of  claim 5  wherein a plasma concentration of celecoxib of at least about 400 ng/ml is attained not later than about 30 minutes after oral administration.  
     
     
         7 . The method of  claim 1  wherein a plasma concentration of celecoxib of at least about 250 ng/ml is attained not later than about 15 minutes after oral administration.  
     
     
         8 . The method of  claim 7  wherein a plasma concentration of celecoxib of at least about 300 ng/ml is attained not later than about 15 minutes after oral administration.  
     
     
         9 . The method of  claim 1  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 1.25 hours.  
     
     
         10 . The method of  claim 9  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 1 hour.  
     
     
         11 . The method of  claim 1  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 50% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         12 . The method of  claim 11  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 33% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         13 . The method of  claim 2  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 25% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         14 . The method of  claim 1  wherein the celecoxib is formulated as an ultra-fine dispersion or solution in a liquid medium.  
     
     
         15 . The method of  claim 1  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 10 μm.  
     
     
         16 . The method of  claim 15  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 2 μm.  
     
     
         17 . The method of  claim 16  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 1 μm.  
     
     
         18 . The method of  claim 1  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 100 nm to about 800 nm.  
     
     
         19 . The method of  claim 18  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 150 nm to about 600 nm.  
     
     
         20 . The method of  claim 19  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 200 nm to about 400 nm.  
     
     
         21 . The method of  claim 1  wherein the celecoxib is formulated as solid particles having a D 25  particle size of about 450 nm to about 1000 nm.  
     
     
         22 . The method of  claim 1  wherein the celecoxib is formulated as solid particles wherein about 25% to 100% by weight of the solid particles have a particle size of about 450 nm to about 1000 nm.  
     
     
         23 . The method of  claim 1  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 450 nm to about 1000 nm.  
     
     
         24  The method of  claim 1  wherein the celecoxib is formulated by dissolving the celecoxib in a suitable solvent and adding the resulting solution to an aqueous liquid to form a fine suspension, and wherein the suspension is administered to the subject not more than about 15 minutes after preparation.  
     
     
         25 . The method of  claim 1  wherein the celecoxib is formulated in solution in a pharmaceutically acceptable solvent.  
     
     
         26 . The method of  claim 25  wherein the solvent is polyethylene glycol.  
     
     
         27 . The method of  claim 25  wherein the celecoxib formulation is encapsulated as a unit dosage form having a capsule wall.  
     
     
         28 . The method of  claim 27  wherein the wall comprises gelatin.  
     
     
         29 . The method of  claim 27  wherein the wall comprises hydroxypropylmethylcellulose.  
     
     
         30 . The method of  claim 1  that comprises combination therapy with one or more drugs selected from opioids and other analgesics.  
     
     
         31 . The method of  claim 1  that comprises combination therapy with an opioid compound selected from codeine, meperidine, morphine and derivatives thereof.  
     
     
         32 . The method of  claim 1  wherein the subject suffers from headache or migraine and wherein there is further orally administered to the subject a vasomodulator, the celecoxib composition and the vasomodulator being administered in total and relative amounts effective to relieve pain in the headache or migraine.  
     
     
         33 . The method of  claim 32  wherein the vasomodulator is coformulated with the celecoxib composition.  
     
     
         34 . The method of  claim 1  wherein the subject suffers from headache or migraine and wherein there is further orally administered to the subject an alkylxanthine compound, the celecoxib composition and the alkylxanthine compound being administered in total and relative amounts effective to relieve pain in the headache or migraine.  
     
     
         35 . The method of  claim 34  wherein the alkylxanthine compound is coformulated with the celecoxib composition.  
     
     
         36 . The method of  claim 34  wherein the alkylxanthine compound is selected from caffeine, theophylline and theobromine.  
     
     
         37 . The method of  claim 36  wherein the alkylxanthine compound is caffeine  
     
     
         38 . A therapeutic method for rapid pain relief in a mammalian subject in need thereof, the method comprising orally administering to the subject, a composition comprising celecoxib in a formulation which provides an effective pain-relieving plasma concentration of at least about 250 ng/ml not later than about 30 minutes after oral administration.  
     
     
         39 . The method of  claim 38  wherein the composition is administered in an amount providing about 50 to about 400 mg celecoxib.  
     
     
         40 . The method of  claim 39  wherein the composition is administered in an amount providing about 100 to about 275 mg celecoxib.  
     
     
         41 . The method of  claim 38  wherein the mammalian subject is a human subject.  
     
     
         42 . The method of  claim 38  wherein a plasma concentration of celecoxib of at least about 300 ng/ml is attained not later than about 30 minutes after oral administration.  
     
     
         43 . The method of  claim 42  wherein a plasma concentration of celecoxib of at least about 400 ng/ml is attained not later than about 30 minutes after oral administration.  
     
     
         44 . The method of  claim 38  wherein a plasma concentration of celecoxib of at least about 250 ng/ml is attained not later than about 15 minutes after oral administration.  
     
     
         45 . The method of  claim 44  wherein a plasma concentration of celecoxib of at least about 300 ng/ml is attained not later than about 15 minutes after oral administration.  
     
     
         46 . The method of  claim 38  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 1.25 hours.  
     
     
         47 . The method of  claim 46  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 1 hour.  
     
     
         48 . The method of  claim 38  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 50% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         49 . The method of  claim 48  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 33% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         50 . The method of  claim 49  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 25% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         51 . The method of  claim 38  wherein the celecoxib is formulated as an ultra-fine dispersion or solution in a liquid medium.  
     
     
         52 . The method of  claim 38  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 10 μm.  
     
     
         53 . The method of  claim 52  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 2 μm.  
     
     
         54 . The method of  claim 53  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 1 μm.  
     
     
         55 . The method of  claim 38  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 100 nm to about 800 nm.  
     
     
         56 . The method of  claim 55  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 150 nm to about 600 nm.  
     
     
         57 . The method of  claim 56  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 200 nm to about 400 nm.  
     
     
         58 . The method of  claim 38  wherein the celecoxib is formulated as solid particles having a D 25  particle size of about 450 nm to about 1000 nm.  
     
     
         59 . The method of  claim 38  wherein the celecoxib is formulated as solid particles wherein about 25% to 100% by weight of the solid particles have a particle size of about 450 nm to about 1000 nm.  
     
     
         60 . The method of  claim 38  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 450 nm to about 1000 nm.  
     
     
         61 . The method of  claim 38  wherein the celecoxib is formulated by dissolving the celecoxib in a suitable solvent and adding the resulting solution to an aqueous liquid to form a fine suspension, and wherein the suspension is administered to the subject not more than about 15 minutes after preparation.  
     
     
         62 . The method of  claim 38  wherein the celecoxib is formulated in solution in a pharmaceutically acceptable solvent.  
     
     
         63 . The method of  claim 62  wherein the solvent is polyethylene glycol.  
     
     
         64 . The method of  claim 62  wherein the celecoxib formulation is encapsulated as a unit dosage form having a capsule wall.  
     
     
         65 . The method of  claim 64  wherein the wall comprises gelatin.  
     
     
         66 . The method of  claim 64  wherein the wall comprises hydroxypropylmethylcellulose.  
     
     
         67 . The method of  claim 38  that comprises combination therapy with one or more drugs selected from opioids and other analgesics.  
     
     
         68 . The method of  claim 38  that comprises combination therapy with an opioid compound selected from codeine, meperidine, morphine and derivatives thereof.  
     
     
         69 . The method of  claim 38  wherein the subject suffers from headache or migraine and wherein there is further orally administered to the subject a vasomodulator, the celecoxib composition and the vasomodulator being administered in total and relative amounts effective to relieve pain in the headache or migraine.  
     
     
         70 . The method of  claim 69  wherein the vasomodulator is coformulated with the celecoxib composition.  
     
     
         71 . The method of  claim 38  wherein the subject suffers from headache or migraine and wherein there is further orally administered to the subject an alkylxanthine compound, the celecoxib composition and the alkylxanthine compound being administered in total and relative amounts effective to relieve pain in the headache or migraine.  
     
     
         72 . The method of  claim 71  wherein the alkylxanthine compound is coformulated with the celecoxib composition.  
     
     
         73 . The method of  claim 71  wherein the alkylxanthine compound is selected from caffeine, theophylline and theobromine.  
     
     
         74 . The method of  claim 73  wherein the alkylxanthine compound is caffeine  
     
     
         75 . A therapeutic method for analgesia in a mammalian subject in need thereof, the method comprising orally administering to the subject, a composition comprising celecoxib in a formulation which provides detectable pain relief not later than about 30 minutes after oral administration.  
     
     
         76 . The method of  claim 75  wherein the composition is administered in an amount providing about 50 to about 400 mg celecoxib.  
     
     
         77 . The method of  claim 75  wherein the composition is administered in an amount providing about 100 to about 275 mg celecoxib.  
     
     
         78 . The method of  claim 75  wherein the mammalian subject is a human subject.  
     
     
         79 . The method of  claim 75  wherein a plasma concentration of celecoxib of at least about 300 ng/ml is attained not later than about 30 minutes after oral administration.  
     
     
         80 . The method of  claim 75  wherein a plasma concentration of celecoxib of at least about 400 ng/ml is attained not later than about 30 minutes after oral administration.  
     
     
         81 . The method of  claim 81  wherein a plasma concentration of celecoxib of at least about 250 ng/ml is attained not later than about 15 minutes after oral administration.  
     
     
         82 . The method of  claim 75  wherein a plasma concentration of celecoxib of at least about 300 ng/ml is attained not later than about 15 minutes after oral administration.  
     
     
         83 . The method of  claim 83  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 1.25 hours.  
     
     
         84 . The method of  claim 75  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 1 hour.  
     
     
         85 . The method of  claim 75  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 50% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         86 . The method of  claim 75  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 33% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         87 . The method of  claim 86  wherein the celecoxib is formulated such that it exhibits a T max  not greater than about 25% of the T max  exhibited by a standard commercial formulation of celecoxib.  
     
     
         88 . The method of  claim 75  wherein the celecoxib is formulated as an ultra-fine dispersion or solution in a liquid medium.  
     
     
         89 . The method of  claim 75  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 10 μm.  
     
     
         90 . The method of  claim 89  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 2 μm.  
     
     
         91 . The method of  claim 90  wherein the celecoxib is formulated as solid particles having a D 90  particle size of less than about 1 μm.  
     
     
         92 . The method of  claim 75  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 100 nm to about 800 nm.  
     
     
         93 . The method of  claim 92  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 150 nm to about 600 nm.  
     
     
         94 . The method of  claim 75  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 200 nm to about 400 nm.  
     
     
         95 . The method of  claim 75  wherein the celecoxib is formulated as solid particles having a D 25  particle size of about 450 nm to about 1000 nm.  
     
     
         96 . The method of  claim 75  wherein the celecoxib is formulated as solid particles wherein about 25% to 100% by weight of the solid particles have a particle size of about 450 nm to about 1000 nm.  
     
     
         97 . The method of  claim 75  wherein the celecoxib is formulated as solid particles having a weight average particle size of about 450 nm to about 1000 nm.  
     
     
         98 . The method of  claim 75  wherein the celecoxib is formulated by dissolving the celecoxib in a suitable solvent and adding the resulting solution to an aqueous liquid to form a fine suspension, and wherein the suspension is administered to the subject not more than about 15 minutes after preparation.  
     
     
         99 . The method of  claim 75  wherein the celecoxib is formulated in solution in a pharmaceutically acceptable solvent.  
     
     
         100 . The method of  claim 99  wherein the solvent is polyethylene glycol.  
     
     
         101 . The method of  claim 99  wherein the celecoxib formulation is encapsulated as a unit dosage form having a capsule wall.  
     
     
         102 . The method of  claim 101  wherein the wall comprises gelatin.  
     
     
         103 . The method of  claim 101  wherein the wall comprises hydroxypropylmethylcellulose.  
     
     
         104 . The method of  claim 75  that comprises combination therapy with one or more drugs selected from opioids and other analgesics.  
     
     
         105 . The method of  claim 75  that comprises combination therapy with an opioid compound selected from codeine, meperidine, morphine and derivatives thereof.  
     
     
         106 . The method of  claim 75  wherein the subject suffers from headache or migraine and wherein there is further orally administered to the subject a vasomodulator, the celecoxib composition and the vasomodulator being administered in total and relative amounts effective to relieve pain in the headache or migraine.  
     
     
         107 . The method of  claim 106  wherein the vasomodulator is coformulated with the celecoxib composition.  
     
     
         108 . The method of  claim 75  wherein the subject suffers from headache or migraine and wherein there is further orally administered to the subject an alkylxanthine compound, the celecoxib composition and the alkylxanthine compound being administered in total and relative amounts effective to relieve pain in the headache or migraine.  
     
     
         109 . The method of  claim 108  wherein the alkylxanthine compound is coformulated with the celecoxib composition.  
     
     
         110 . The method of  claim 108  wherein the akylxanthine compound is selected from caffeine, theophylline and theobromine.  
     
     
         111 . The method of  claim 110  wherein the alkylxanthine compound is caffeine.  
     
     
         112 . The method of  claim 75  wherein the celecoxib formulation provides detectable pain relief not later than about 15 minutes after oral administration  
     
     
         113 . A method of use of celecoxib, formulated in such a way as to provide, when tested in an effective pain-relieving amount in fasting humans in accordance with standard pharmacokinetic practice, a blood plasma concentration profile of celecoxib in which a concentration of about 250 ng/ml is attained not later than about 30 minutes after oral administration, in preparation of a medicament for rapid relief of pain.  
     
     
         114 . A pharmaceutical composition comprising a formulation of solid particulate celecoxib having a weight average particle size of about 100 nm to about 800 nm.  
     
     
         115 . A composition for orally administering to a mammalian subject in need of analgesia, the composition comprising an effective pain-relieving amount of celecoxib formulated in such a way as to provide, when tested in fasting humans in accordance with standard pharmacokinetic practice, a blood plasma concentration profile of celecoxib in which a concentration of at least about 250 ng/ml is attained not later than about 30 minutes after oral administration.  
     
     
         116 . A composition for rapid pain relief in a mammalian subject in need thereof, the composition comprising celecoxib in an oral formulation which provides an effective pain-relieving plasma concentration of at least about 250 ng/ml not later than about 30 minutes after oral administration.  
     
     
         117 . A composition for analgesia in a mammalian subject in need thereof, the composition comprising an oral formulation which provides detectable pain relief not later than about 30 minutes after oral administration.  
     
     
         118 . The composition of  claim 117  wherein the celecoxib formulation provides detectable pain relief not later than about 15 minutes after oral administration.