Therapeutic window for citrulline therapy

A method for maintaining the coupling of endothelial nitric oxide synthase (eNOS) to reduce the incidence or severity of cardiopulmonary bypass-induced pulmonary injury due to free radical formation in a patient during cardiopulmonary bypass comprising administering an effective amount of citrulline to the patient, such that the plasma citrulline concentration is maintained between 80-180 μM.

A method for maintaining the coupling of endothelial nitric oxide synthase (eNOS) to reduce the incidence or severity of sickle cell disease, especially sickle cell crisis, subarachnoid hemorrhage, bronchopulmonary dysplasia, pulmonary hypertension, (including primary and secondary), hyperammonemia, asthma, other urea cycle related conditions, hepatitis (including hepatitis A, B and C), cirrhosis, sclerosis, asthma, especially acute asthma attack, Acute Respiratory Distress Syndrome (ARDS), bone marrow transplant toxicity in a subject undergoing bone marrow transplant, chemotherapy or other pharmaceutical therapy, sepsis, ethnic specific endothelial dysfunction, erectile dysfunction, necrotizing enterocolitis (NEC), increased oxidative stress, sepsis, hypoxia, hepatotoxin exposure, and/or combinations thereof, said method comprising administering an effective amount of citrulline to the patient, such that the plasma citrulline concentration is maintained between 80-180 μM.