Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects
First Claim
1. A method of enhancing dextromethorphan plasma levels in a human being, comprising co-administering a bupropion, a hydroxybupropion, a threohydroxybupropion, or a erythrohydroxybupropion, with a dextromethorphan, to the human being, for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, and the dextromethorphan, are the sole active agents administered to the human being, wherein the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion is administered in an amount that results in a Cmax of dextromethorphan that is at least about 35 ng/mL, and wherein, on the eighth day that the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, and the dextromethorphan, are co-administered, the Cmax of dextromethorphan is at least about 15 times the Cmax of dextromethorphan that would result from administering the same amount of the dextromethorphan without the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion.
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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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Citations
29 Claims
- 1. A method of enhancing dextromethorphan plasma levels in a human being, comprising co-administering a bupropion, a hydroxybupropion, a threohydroxybupropion, or a erythrohydroxybupropion, with a dextromethorphan, to the human being, for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, and the dextromethorphan, are the sole active agents administered to the human being, wherein the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion is administered in an amount that results in a Cmax of dextromethorphan that is at least about 35 ng/mL, and wherein, on the eighth day that the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, and the dextromethorphan, are co-administered, the Cmax of dextromethorphan is at least about 15 times the Cmax of dextromethorphan that would result from administering the same amount of the dextromethorphan without the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion.
- 15. A method of increasing dextromethorphan plasma levels in a human being, comprising co-administering a bupropion, a hydroxybupropion, a threohydroxybupropion, or a erythrohydroxybupropion, with a dextromethorphan, to the human being for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, and the dextromethorphan, are the sole active agents administered to the human being, wherein the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion is administered in an amount that results in a Cmin of dextromethorphan that is at least about 20 ng/mL, and wherein, on the eighth day that the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, and the dextromethorphan, are co-administered, the Cmax of dextromethorphan is at least about 15 times the Cmax of dextromethorphan that would result from administering the same amount of dextromethorphan without the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion.
- 20. A method of increasing dextromethorphan plasma levels in a human being, comprising co-administering a bupropion, a hydroxybupropion, a threohydroxybupropion, or a erythrohydroxybupropion, with a dextromethorphan, to the human being for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, and the dextromethorphan, are the sole active agents administered to the human being, wherein the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion is administered in an amount that results in a Cavg of dextromethorphan, over the period between two separate and consecutive administrations of the dextromethorphan, that is at least about 25 ng/mL, and wherein, on the eighth day that the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, and the dextromethorphan, are co-administered, the Cmax of dextromethorphan is at least about 20 times the Cmax of dextromethorphan that would result from administering the same amount of dextromethorphan without the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion.
Specification