Pharmaceutical formulations of potassium atp channel openers and uses thereof

Abstract

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

1 .- 17 . (canceled) 
   
   
       18 . A controlled release pharmaceutical formulation comprising a K ATP  channel opener of formula II or formula III and a pharmaceutically active agent other than said K ATP  channel opener. 
   
   
       19 . The formulation of  claim 18 , wherein said pharmaceutically active agent other than said K ATP  channel opener is an agent useful for the treatment of a condition selected from the group consisting of obesity, prediabetes, diabetes, hypertension, depression, elevated cholesterol, fluid retention, other obesity associated comorbidities, ischemic and reperfusion injury, epilepsy, schizophrenia, mania, and other psychotic conditions. 
   
   
       20 .- 48 . (canceled) 
   
   
       49 . A pharmaceutical formulation comprising a K ATP  channel opener of formula II or formula III and a pharmaceutically active agent other than said K ATP  channel opener. 
   
   
       50 . The formulation of  claim 49 , wherein said pharmaceutically active agent other than said K ATP  channel opener is an agent useful for the treatment of a condition selected from the group consisting of obesity, prediabetes, diabetes, hypertension, depression, elevated cholesterol, fluid retention, other obesity associated comorbidities, ischemic and reperfusion injury, epilepsy, schizophrenia, mania, and other psychotic conditions. 
   
   
       51 . The formulation of  claim 18 , wherein said pharmaceutically active agent other than said K ATP  channel opener comprises a cholesterol-lowering drug. 
   
   
       52 . The formulation of  claim 51 , wherein said cholesterol-lowering drug comprises a statin selected from the group consisting of pravastatin, simvastatin, atorvastatin, fluvastatin, rosuvastatin, and lovastatin. 
   
   
       53 . The formulation of  claim 18  for a single administration that contains between 10 and 100 mg of said K ATP  channel opener. 
   
   
       54 . The formulation of  claim 18  for a single administration that contains between 100 and 200 mg of said K ATP  channel opener. 
   
   
       55 . The formulation of  claim 18  for a single administration that contains between 200 and 300 mg of said K ATP  channel opener. 
   
   
       56 . The formulation of  claim 18  for a single administration that contains between 300 and 500 mg of said K ATP  channel opener. 
   
   
       57 . The formulation of  claim 18  for a single administration that contains between 500 mg and 2000 mg of said K ATP  channel opener. 
   
   
       58 . The formulation of  claim 18 , wherein said K ATP  channel opener is diazoxide. 
   
   
       59 . The formulation of  claim 49 , wherein said pharmaceutically active agent other than said K ATP  channel opener comprises a cholesterol-lowering drug. 
   
   
       60 . The formulation of  claim 59 , wherein said cholesterol-lowering drug comprises a statin selected from the group consisting of pravastatin, simvastatin, atorvastatin, fluvastatin, rosuvastatin, and lovastatin. 
   
   
       61 . The formulation of  claim 49  for a single administration that contains between 10 and 100 mg of said K ATP  channel opener. 
   
   
       62 . The formulation of  claim 49  for a single administration that contains between 100 and 200 mg of said K ATP  channel opener. 
   
   
       63 . The formulation of  claim 49  for a single administration that contains between 200 and 300 mg of said K ATP  channel opener. 
   
   
       64 . The formulation of  claim 49  for a single administration that contains between 300 and 500 mg of said K ATP  channel opener. 
   
   
       65 . The formulation of  claim 49  for a single administration that contains between 500 mg and 2000 mg of said K ATP  channel opener. 
   
   
       66 . The formulation of  claim 49 , wherein said K ATP  channel opener is diazoxide.