Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects
First Claim
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1. A method of correcting extensive metabolism of dextromethorphan in a human subject in need thereof, comprising co-administering to the human subject once a day for at least eight consecutive days or twice a day for at least eight consecutive days:
- 1) a hydroxybupropion, a threohydroxybupropion, an erythrohydroxybupropion or a bupropion; and
2) a dextromethorphan;
wherein the human subject is an extensive metabolizer of the dextromethorphan in need of treatment with dextromethorphan, and wherein the daily dose of the dextromethorphan is about 40 mg to about 350 mg, and co-administration of the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion, and the dextromethorphan results in a first AUC0-24 of the dextromethorphan on Day 8 that is at least about 50 ng·
hr/mL, and the first AUC0-24 of the dextromethorphan is at least about 20 times a second AUC0-24 of the dextromethorphan on Day 8 that would result from administering the daily dose of the dextromethorphan without the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion to the human subject for 8 consecutive days.
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Abstract
This disclosure relates to methods administering various compounds in conjunction with dextromethorphan to a human being. Dosage forms, drug delivery systems, and methods related to dextromethorphan or dextrorphan and bupropion, hydroxybupropion, erythrohydroxybupropion, threohydroxybupropion, or a metabolite or prodrug of any of these compounds are also disclosed.
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30 Claims
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1. A method of correcting extensive metabolism of dextromethorphan in a human subject in need thereof, comprising co-administering to the human subject once a day for at least eight consecutive days or twice a day for at least eight consecutive days:
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1) a hydroxybupropion, a threohydroxybupropion, an erythrohydroxybupropion or a bupropion; and 2) a dextromethorphan; wherein the human subject is an extensive metabolizer of the dextromethorphan in need of treatment with dextromethorphan, and wherein the daily dose of the dextromethorphan is about 40 mg to about 350 mg, and co-administration of the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion, and the dextromethorphan results in a first AUC0-24 of the dextromethorphan on Day 8 that is at least about 50 ng·
hr/mL, and the first AUC0-24 of the dextromethorphan is at least about 20 times a second AUC0-24 of the dextromethorphan on Day 8 that would result from administering the daily dose of the dextromethorphan without the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion to the human subject for 8 consecutive days. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
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Specification