Plasma L-citrulline concentrations in L-arginine supplemented healthy dogs

Introduction: To determine whether oral L-arginine increases plasma [L citrulline] in dogs. Animals: Eleven healthy staff -owned dogs were used in this study. Materials and methods: Dogs (n = 3) were given L-arginine (50mg/kg PO q8h) for 7 days, and plasma [L-arginine] and [L-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100rng/kg Larginine PO q8h for 7 days, and [L-arginine] and [L-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). Results: Plasma [L-arginine] and [L-citrulline] peaked at T4 his on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [L-arginine] and a 25-30% increase in [L-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [L-arginine] increased from a BL median of 160.1 pM (range, 100.2-231.4 OA) to a peak of 417.4 AM (206.5-807.3 jiM) at T4 hrs, and plasma [L-citrulline] increased from a BL median of 87.8 IA (59.1-117.1 M). to peak of 102.2 jiM (47.4-192.6 1.1M) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [L-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [L-citrulline]. No adverse effects on heart rate or blood pressure were noted. Conclusions: Oral L-arginine dosage of 100mg/kg q8h doubles plasma [L-arginine] in healthy dogs, but conversion to L-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. (C) 2017 Elsevier B.V. All rights reserved.