Fk506 for the treatment of pulmonary arterial hypertension

Abstract

A method for reducing pulmonary hypertension in a mammal that employs FK506 is provided. In certain embodiments, the method comprises administering FK506 to a mammal having pulmonary arterial hypertension associated with defective MBPR2 signaling at a dosage sufficient to reduce blood pressure in the pulmonary artery of the mammal.

1 - 8 . (canceled) 
     
     
         9 . A method of treating pulmonary arterial hypertension in a patient in need thereof, the method comprising: administering FK506 to the patient at a daily dosage of 0.002 mg/kg of the patient's weight to 0.05 mg/kg of the patient's weight. 
     
     
         10 . The method of  claim 9 , wherein the dosage provides an FK506 blood concentration of 0.05 ng/mL to 1 ng/mL. 
     
     
         11 . The method of  claim 9 , wherein the dosage provides an FK506 blood concentration of 0.1 ng/mL to 0.2 ng/mL. 
     
     
         12 . The method of  claim 9 , wherein the dosage provides an FK506 blood concentration of 0.2 ng/mL to 2 ng/mL. 
     
     
         13 . The method of  claim 9 , wherein the dosage provides an FK506 blood concentration of 1.5 ng/mL to 2.5 ng/mL. 
     
     
         14 . The method of  claim 9 , wherein the dosage provides an FK506 blood concentration of 3 ng/mL to 5 ng/mL. 
     
     
         15 . The method of  claim 9 , wherein the dosage provides an FK506 blood concentration of FK506 of below 1 ng/mL. 
     
     
         16 . The method of  claim 9 , further comprising administering the FK506 in combination with a therapeutically effective amount of at least one additional active compound. 
     
     
         17 . The method of  claim 16  where the at least one additional active compound is one or more selected from the following list: sildenafil, bosentan, ambrisentan, epoprostenol, tadalafil, treprostinil iloprost, treprostinil, isosorbide dinitrate, or isosorbide dinitrate. 
     
     
         18 . The method of  claim 16  where the at least one additional active compound is one or more selected from the following list: prostacyclin analogues, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, high-dose calcium channel blockers, antigoagulants, diuretics and antiproliferative agents. 
     
     
         19 . A method of treating pulmonary arterial hypertension in a patient in need thereof, the method comprising: administering FK506 to the patient at a daily dosage of 0.001 mg/kg of the patient's weight to 0.01 mg/kg of the patient's weight. 
     
     
         20 . The method of  claim 19 , wherein the dosage provides an FK506 blood concentration of 0.05 ng/mL to 1 ng/mL. 
     
     
         21 . The method of  claim 19 , wherein the dosage provides an FK506 blood concentration of FK506 of below 1 ng/mL.