Ornithine alpha-ketoglutarate (OKG) has been successfully used as an enteral supplement in the treatment of catabolic states, including
burn injury. However, specific questions remain unanswered concerning
burn patients, including OKG metabolism and metabolite production, appropriate mode of administration, and dose. We thus performed a kinetic study and followed plasma
ornithine and OKG metabolite concentrations on day 7 postburn in 42 (35 men, 7 women) consecutive
burn patients aged 33 +/- 2 y with a mean (+/-SEM) total
burn surface area (TBSA) of 31 +/- 1%. Patients were randomly assigned to receive OKG as a single bolus (10 g; n = 13) or in the form of a continuous gastric infusion (10, 20, or 30 g/d over 21 h; n = 13) or an isonitrogenous control (n = 16). Plasma pharmacokinetics of
ornithine followed a one-compartment model with first-order input (r = 0.993, P < 0.005). OKG was extensively metabolized in these patients (absorption constant = 0.028 min-1, elimination half-life = 89 min), with the production of
glutamine,
arginine, and
proline;
proline was quantitatively the main metabolite [in OKG bolus, area under the curve (AUC)0-7h:
proline, 41.4 +/- 5.6 mmol.min/
L; glutamine, 20.4 +/- 5.7 mmol.min/L; and
arginine, 7.3 +/- 1.9 mmol.min/L].
Proline production was dose-dependent and quantitatively similar between modes of OKG administration.
Glutamine and
arginine production were not dose-dependent and were higher in the bolus group than in the infusion group. Overall, the bolus mode of OKG administration appeared to be associated with higher metabolite production compared with continuous infusion in
burn patients, especially for
glutamine and
arginine.