Metabolism of Ornithine Phenylacetate

The study involves 1 screening visit of approximately 1 hour and 4 study days of approximately 10 hours. The subject will be asked to arrive in the fasted state on all study days. Fasting prior to screening is not required. On the screening day, body weight and height will be measured and Dual-energy X-ray absorptiometry (DXA) will be performed to measure body composition. After 4 hours subjects received a continuous intravenous infusion with OP in a dosage of 1 g /h. Next to the stable tracers provided to determine OP metabolism, stable tracers of phenylalanine (PHE) and tyrosine (TYR) may be provided to determine the effect of OP on protein metabolism at plasma and muscle tissue level. This required 2 muscle biopsies and on 2 study days 1 set of stable tracer pulses.

Inclusion criteria

healthy subjects:

• Healthy male & female according to the investigator's or appointed staff's judgment
• Age 40-70 years (to be comparable with patients with liver cirrhosis: average 54.1 +/- 9.4 years)

Exclusion criteria

• Metabolic diseases including diabetes and hepatic or renal disorders
• Presence of acute illness or metabolically unstable chronic illness
• Failure to give informed consent
• (Possible) pregnancy
• Any other condition according to the PI or nurse that would interfere with the study or safety of the patient or influence the results
• Unwilling to stop taking nutritional protein supplements within 5 days before test day
• History of hypo- or hyper-coagulation disorders, including use of a Coumadin derivative, history of deep venous thrombosis (DVT), or pulmonary embolism (PE) at any point in lifetime
• Currently taking anti-thrombotics (i.e. medical indication) and cannot stop for 3-7 days prior to test days
• Allergy to local anesthetic