Impact of IV arginine therapy on plasma. (A) Arginine and (B) kyotorphin concentrations (μM) over 8 hours and daily. Both plasma arginine and kyotorphin levels peaked within 30 minutes of completion of IV arginine infusion delivered over 30 minutes. Pooled data from the 3 dosing arms are represented, as there was no significant difference in the peak concentration across the study arms. For the 8-hour pK study, plasma arginine concentration troughs by 4 hours but remains significantly above baseline through 8 hours (P = .01) and day 2 (P = .01). Plasma kyotorphin levels were significantly elevated between 1 to 2 hours (P = .004), before dropping toward baseline. Morning blood draws occurred at ∼8 AM daily, >6 hours from the last arginine infusion, representing a trough in plasma arginine and kyotorphin levels. The participants available for daily blood analysis varied based on the clinical resolution of their vaso-occlusive pain and discharge day; there were 13 individuals analyzed on day 1, 11 individuals on day 2, 7 individuals on day 3, 6 individuals on day 4, 4 individuals on day 5, and 3 individuals on day 6.