Pharmaceutical formulations of potassium atp channel openers and uses thereof

Abstract

Provided are immediate or prolonged administration of certain potassium ATP (KATP) channel openers to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving KATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of KATP channel openers that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering KATP channel openers with other drugs to treat diseases of humans and animals.

1 - 20 . (canceled) 
     
     
         21 . A method of treating hyperphagia associated with Prader Willi Syndrome in a subject in need thereof, said method comprising administering a pharmaceutical formulation of diazoxide to the subject in combination with a pharmaceutically active agent,
 wherein the pharmaceutically active agent is selected from the group consisting of an anti-psychotic drug, a depression treating drug, a tranquilizer, an obesity treating drug, a diabetes treating drug, a cholesterol lowering drug, a hypertension treating drug, a diuretic, and a drug to treat inflammation or pain.   
     
     
         22 . The method of  claim 21 , wherein the anti-psychotic drug is selected from the group consisting of lithium, carbamazepine, valproic acid, lamotrigine, paloproxidol, perphenazine, thioridazine, risperidone, clozapine, olanzapine and chlorpromazine. 
     
     
         23 . The method of  claim 21 , wherein the depression treating drug is selected from the group consisting of citalopram hydrobromide, escitalopram hydrobromide, fluvoxamine maleate, paroxetine hydrochloride, fluoxetine hydrochloride, setraline hydrochloride, amitriptyline hydrochloride, desipramine hydrochloride, nortriptyline hydrochloride, duloxetine hydrochloride, venlafaxine hydrochloride, phenelzine sulfate, bupropion hydrochloride, and mirtazapine. 
     
     
         24 . The method of  claim 21 , wherein the depression treating drug is a monoamine oxidase inhibitor, a tricyclic antidepressant, or a tetracyclic antidepressant. 
     
     
         25 . The method of  claim 24 , wherein the monoamine oxidase inhibitor is selected from the group consisting of isocarboxazid, phenelzine sulfate and tranylcypromine sulfate. 
     
     
         26 . The method of  claim 24 , wherein the tricyclic antidepressant is selected from the group consisting of doxepin, clomipramine, amitriptyline, maproiline, desipromine, nortryptyline, desipramine, doxepin, trimipramine, imipramine and protryptyline. 
     
     
         27 . The method of  claim 24 , wherein the tetracyclic antidepressant is selected from the group consisting of mianserin, mirtazapine, maprotiline, oxaprotline, delequamine, levoprotline, triflucarbine, setiptiline, lortalaline, azipramine, aptazapine maleate and pirlindole. 
     
     
         28 . The method of  claim 21 , wherein the obesity treating drug is selected from the group consisting of sibutramine hydrochloride, orlistat, phentermine hydrochloride, phentermine resin complex, zonisamide, topiramate, naltrexone hydrochloride, rimonabant, ADP356, ATL962, AOD9604, short-acting bromocriptine, adiponectin, extendin-4, and liraglutide. 
     
     
         29 . The method of  claim 21 , wherein the diabetes drug is selected from the group consisting of acarbose, miglitol, metformin hydrochloride, repaglinide, nateglinide, rosiglitizone, and metaglidasen. 
     
     
         30 . The method of  claim 21 , wherein the cholesterol lowering drug is selected from the group consisting of pravastatin, simvastatin, atorvastatin, fluvastatin, rosuvastatin, and lovastatin. 
     
     
         31 . The method of  claim 21 , wherein the hypertension treating drug is selected from the group consisting of enalapril maleate, captopril, lisinopril, benzaepril hydrochloride, quinapril hydrochloride, peridopril erbumine, ramipril, trandolapril, fosinopril sodium, moexipril hydrochloride, losartan potassium, irbesartan, valsartan, candesartan cilexetil, olmesartan medoxamil, telmisartan, eprosartan mesylate, atenolol, propranolol hydrochloride, metoprolol tartrate, metoprolol succinate, metoprolol fumarate, nadolol, betaxolol hydrochloride, acebutolol hydrochloride, pindolol, bisoprolol fumarate, nifedipine, felodipine, amlodipine besylate, nicardipine, nisoldipine, terazosin hydrochloride, doxasoxin mesylate, prazosin hydrochloride, and alfuzosin hydrochloride. 
     
     
         32 . The method of  claim 21 , wherein the diuretic is selected from the group consisting of amiloride hydrochloride, spironolactone, triamterene, bumetanide, ethacrynic acid or ethacrynate sodium, tosemide, chlorthalidone, indapamide, hydrochlorothiazide, chlorothiazide, bendroflumethiazide, hydroflumethiazide, mythyclothiazide, and polythiazide. 
     
     
         33 . The method of  claim 21 , wherein the drug to treat inflammation or pain is selected from the group consisting of aspirin, tramadol hydrochloride, gabapentin, acetominophen, carbamazepine, ibuprofen, ketoprofen, fenprofen sodium, flurbiprofen sodium, flurbiprofen, and combinations of the foregoing with a steroid or aspirin. 
     
     
         34 . The method of  claim 21 , wherein the pharmaceutical formulation of diazoxide is orally administered. 
     
     
         35 . The method of  claim 34 , wherein the pharmaceutical formulation of diazoxide includes at least one excipient which affects the rate of release of diazoxide. 
     
     
         36 . The method of  claim 34 , wherein the pharmaceutical formulation of diazoxide includes at least one excipient that delays release of diazoxide. 
     
     
         37 . The method of  claim 34 , wherein the pharmaceutical formulation of diazoxide is administered twice per day. 
     
     
         38 . The method of  claim 34 , wherein the pharmaceutical formulation of diazoxide is administered once per day. 
     
     
         39 . The method of  claim 21 , wherein the pharmaceutical formulation of diazoxide is separate from the pharmaceutically active agent. 
     
     
         40 . The method of  claim 21 , wherein the subject is administered a mixture of the pharmaceutical formulation of the diazoxide and the pharmaceutically active agent.