Patent EA-005158-B1 (EA)
Title: Use of cyp2d6
Inventor: OBACH RONALD SCOTT
IPC: A61K31/44
Filed: 2000-03-20
Abstract: 1. A method of administering a drug for which the major clearance mechanism in humans is CYP2D6 (CYP-cytochrome P-450) mediated oxidative biotransformation, or a pharmaceutically acceptable salt thereof, in combination with a CYP2D6 inhibitor, or a pharmaceutically acceptable salt thereof, to a human in need of the intended pharmaceutical activity of such drug, wherein said drug for which the major clearance mechanism in humans is CYP2D6 mediated oxidative biotransformation is selected from the group consisting of an NMDA (N-methyl-D-aspartate) receptor antagonist containing a primary, secondary or tertiary alkylamine moiety and a neuokinin-1 (NK-1) receptor antagonist containing a primary, secondary or tertiary alkylamine moiety and wherein said drug and said CYP2D6 inhibitor are not the same compound. 2. A method according to claim 1 wherein the drug for which the major clearance mechanism in humans is CYP2D6 mediated oxidative biotransformation is selected from the group consisting of a selective serotonin reuptake inhibitor containing a primary, secondary or tertiary alkylamine moiety; an NMDA (N-methyl-D-aspartat) receptor antagonist containing a primary, secondary or tertiary alkylamine moiety; a neurokinin-1 (NK-1) receptor antagonist containing a primary, secondary or tertiary alkylamine moiety; a tricyclic antidepressant containing a primary, secondary or tertiary alkylamine moiety; and pharmaceutically acceptable salts thereof. 3. A method according to claim 1, wherein the drug for which the major clearance mechanism in humans is CYP2D6 mediated oxidative biotransformation, or pharmaceutically acceptable salt thereof, is selected from the group consisting of (2S,3S)-2-phenyl-3-(2-methoxy-5-trifluoromethoxyphenyl) methylamino-piperidine; (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol; sunipetron; and pharmaceutically acceptable salts thereof. 4. A method according to claim 1, wherein the drug for which the major clearance mechanism in humans is CYP2D6 mediated oxidative biotransformation, or pharmaceutically acceptable salt thereof, is selected from the group consisting of mequitazine, tamsulosin, oxybutynin, ritonavir, iloperidone, ibogaine, delavirdine, tolteridine, promethazine, pimozide, epinastine, tramodol, procainamide, methamphetamine, tamoxifen, nicergoline, fluoxetine, alprenolol, amiflamine, amitriptyline, aprindine, brofaromine, buturalol, cinnarizine, clomipramine, codeine, debrisoquine, desipramine, desmethylcitalopram, dexfenfluramine, dextromethorphan, dihydrocodine, dolasetron, encainide, ethylmorphine, flecainide, flunarizine, fluvoxamine, guanoxan, haloperidol, hydrocodone, indoramin, imipramine, maprotiline, methoxyamphetamine, methoxyphenamine, methylenedioxymethamphetamine, metoprolol, mexiletine, mianserin, minaprine, procodeine, nortriptyline, N-propylajmaline, ondansetron, oxycodone, paroxetine, perhexiline, perphenazine, phenformine, promethazine, propafenone, propanolol, risperidone, sparteine, thioridazine, timolol, tomoxetine, tropisetron, venlafaxine, zuclopenthixol, and pharmaceutically acceptable salts thereof. 5. A method according to claim 1, wherein the CYP2D6 inhibitor, or pharmaceutically acceptable salt thereof, is selected from the group consisting of quinidine, ajmalacine, sertraline, venlafaxine, dexmedetomidine, tripennelamine, premethazine, hydroxyzine, halofrintane, chloroquine, moclobemide, and pharmaceutically acceptable salts thereof, and St. John's wort, or an extract or component thereof. 6. A pharmaceutical composition comprising: a) a therapeutically effective amount of a drug for which the major clearance mechanism in humans is CYP2D6 mediated oxidative biotransformation, or a pharmaceutically acceptable salt thereof; (b) an amount of a CYP2D6 inhibitor, or a pharmaceutically acceptable salt thereof, that is effective in treating the disorder or condition for which the drug referred to in "a" is intended to treat; and (c) a pharmaceutically acceptable carrier wherein said drug for which the major clearance mechanism in humans is CYP2D6 mediated oxidative biotransformation is selected from the group consisting of an NMDA (N-methyl-D-aspartate) receptor antagonist containing a primary, secondary or tertiary alkylamine moiety and a neuokinin-1 (NK-1) receptor antagonist containing a primary, secondary or tertiary alkylamine moiety and wherein said drug and said CYP2D6 inhibitor are not the same compound. 7. A pharmaceutical composition according to claim 6, wherein the drug for which the major clearance mechanism in humans is CYP2D6 mediated oxidative biotransformation, or pharmaceutically acceptable salt thereof, that is contained in such pharmaceutical composition is selected from the group consisting of (2S,3S)-2-phenyl-3-(2-methoxy-5-trifluoromethoxy-phenyl) methylaminopiperidine; sunipetron; (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol; and pharmaceutically acceptable salts thereof. 8. A pharmaceutical composition according to claim 6, wherein the drug for which the major clearance mechanism in humans is CYP2D6 mediated oxidative biotransformation, or pharmaceutically acceptable salt thereof, is selected from the group consisting of mequitazine, tamsulosin, oxybutynin, ritonavir, iloperidone, ibogaine, delavirdine, tolteridine, promethazine, pimozide, epinastine, tramodol, procainamide, methamphetamine, tamoxifen, nicergoline, fluoxetine, alprenolol, amiflamine, amitriptyline, aprindine, brofaromine, buturalol, cinnarizine, clomipramine, codeine, debrisoquine, desipramine, desmethylcitalopram, dexfenfluramine, dextromethorphan, dihydrocodine, dolasetron, encainide, ethylmorphine, flecainide, flunarizine, fluvoxamine, guanoxan, haloperidol, hydrocodone, indoramin, imipramine, maprotiline, methoxyamphetamine, methoxyphenamine, methylenedioxymethamphetamine, metoprolol, mexiletine, mianserin, minaprine, procodeine, nortriptyline, N-propylajmaline, ondansetron, oxycodone, paroxetine, perhexiline, perphenazine, phenformine, promethazine, propafenone, propanolol, risperidone, sparteine, thioridazine, timolol, tomoxetine, tropisetron, venlafaxine, zuclopenthixol, and pharmaceutically acceptable salts thereof. 9. A pharmaceutical composition according to claim 6, wherein the CYP2D6 inhibitor, or pharmaceutically acceptable salt thereof, is selected from the group consisting of quinidine, ajmalacine, sertraline, venlafaxine, dexmedetomidine, tripennelamine, premethazine, hydroxyzine, halofrintane, chloroquine, moclobemide, and pharmaceutically acceptable salts thereof. 10. A pharmaceutical composition according to claim 6, wherein the CYP2D6 inhibitor is St. John's wort, or an extract or component thereof.