Methods of colchicine administration
AssigneeHikma Pharmaceuticals LLC
InventorMurray Ducharme
Life of this patent
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Abstract
The invention provides improved methods for coadministration of colchicine with drugs metabolized by CYP3A4 (anciently referred to as cytochrome P450 isozyme 3A4) or the P-glycoprotein transporter, but not both. The method enables non-toxic coadministration of colchicine and the second drug at their ordinary levels safely and effectively without reducing the dose or frequency for either drug.
Claims18
A method of administering a fixed maintenance dose of colchicine in a patient concomitantly administered voriconazole without dose reduction of colchicine, comprising inducing in said patient a pharmacokinetic profile of colchicine selected from:
- a) a pharmacokinetic profile of colchicine comprising a mean Cmax of 2058.2±44.9% pg/mL, a median Tmax of 1.5±35.4% hours, a mean AUCT of 20730.8±36.9% pg·h/mL where T equals 72 hours, a mean AUC∞ of 24100.1±37.3% pg·h/mL, and a mean elimination half life of 31.30 hours±17.0%;
- and
- b) a pharmacokinetic profile of colchicine comprising a Cmax of 1834.9±30.8% pg/mL (geometric least squares means), an AUCT of 19502.6±28.0% pg·h/mL (geometric least squares mean) where T equals 72 hours, and an AUC∞ of 22663.5±27.2% pg·h/mL (geometric least squares mean);
- wherein the mean AUCT or AUCT (geometric least squares mean) of colchicine in the pharmacokinetic profile of the patient is about the same as a mean AUCT or AUCT (geometric least squares mean) of colchicine, respectively, in a pharmacokinetic profile in the patient when colchicine is administered in the same fixed maintenance dose without concomitant administration of voriconazole.
A method of administering a fixed maintenance dose of colchicine to a patient concomitantly administered voriconazole, comprising inducing in the patient following concomitant administration of colchicine and voriconazole a pharmacokinetic profile comprising an AUCT of colchicine that is about 104% to about 110% of an AUCT of colchicine in a pharmacokinetic profile of the patient following administration of the same fixed maintenance dose of colchicine without concomitant administration of voriconazole.
A method of administering a fixed maintenance dose of colchicine to a patient concomitantly administered voriconazole, comprising inducing in the patient following concomitant administration of colchicine and voriconazole a pharmacokinetic profile comprising a geometric least squares mean AUCT of colchicine that is 89% to 133% of the geometric least squares mean AUCT of colchicine in the pharmacokinetic profile of the patient following administration of the same fixed maintenance dose of colchicine without concomitant administration of voriconazole.
A method of administering a fixed maintenance dose of colchicine in a patient concomitantly administered a second compound selected from fluconazole and cimetidine without dose reduction of colchicine, comprising inducing in said patient a pharmacokinetic profile of colchicine selected from:
- (i) when the second compound is fluconazole:
- a) a pharmacokinetic profile of colchicine comprising a mean Cmax of 2299.2±57.6% pg/mL, a median Tmax of 1.38±25.4% hours, a mean AUCT of 21270.7±33.6% pg·h/mL where T equals 72 hours, and a mean elimination half life of 34.51±14.8% hours;
- and
- b) a pharmacokinetic profile of colchicine comprising a Cmax of 2046.3±27.1% pg/mL (geometric least squares means), an AUCT of 20364.2±22.4% pg·h/mL (geometric least squares mean) where T equals 72 hours, and an AUC∞ of 24386.8±22.5% pg·h/mL (geometric least squares mean);
- and
- (ii) when the second compound is cimetidine:
- a) a pharmacokinetic profile of colchicine comprising a mean Cmax of 2108.7±50.2% pg/mL, a median Tmax of 1.03±30.2% hours, a mean AUCT of 18082.1±41.6% pg·h/mL where T equals 72 hours, and a mean elimination half life of 31.54±11.1% hours;
- and
- b) a pharmacokinetic profile of colchicine comprising a Cmax of 1878.1±29.3% pg/mL (geometric least squares means), an AUCT of 16719.0±18.7% pg·h/mL (geometric least squares mean) where T equals 72 hours, and an AUC∞ of 19334.3±19.4% pg·h/mL (geometric least squares mean);
- wherein the mean AUCT or AUCT (geometric least squares mean) of colchicine in the pharmacokinetic profile of the patient is about the same as a mean AUCT or AUCT (geometric least squares mean) of colchicine, respectively, in a pharmacokinetic profile in the patient when colchicine is administered in the same fixed maintenance dose without concomitant administration of the second compound.
Dependencies are inferred from the claim text.