Drug dosing and sample collection
STERILE
Each patient received 12 doses of 60 mg/kg enteral L-citrulline. The L-citrulline was donated by Askeplion Pharmaceuticals, Baltimore, MD, and was provided in a powder form that was solubilized in sterile water to achieve 50 mg/ml concentration. Each participant received 1.2 ml/kg (60 mg/kg) of the solubilized L-citrulline every 6 h ± 30 min (4 times a day) for 72 h. The total daily volume of solubilized L-citrulline was 4.8 ml/kg/d for a total daily L-citrulline dose of 240 mg/kg/d. Each dose of L-citrulline was delivered via an indwelling nasogastric feeding tube thirty minutes prior to a feeding.Two (0.3–0.5 mL) blood samples were collected into EDTA microtainers by heel stick methodology from each infant. The first sample was a pre-dose blood sample collected between 10 min and 6 h before administering the first dose of enteral L-citrulline. The second sample was collected 10 to 30 min before the last (12th) dose of enteral L-citrulline. These sampling times were designed to assess baseline and steady-state trough L-citrulline plasma concentrations.For each infant, we also collected two urine samples via cotton balls placed in their diapers. The first urine sample was collected the day before administering the first enteral dose of L-citrulline. The second sample was collected between 4 and 8 h following the last (12