Pharmacokinetics of Salicylic Acid Following Intravenous and Oral Administration of Sodium Salicylate in Sheep

Abstract

The pharmacokinetics of salicylic acid (SA) in sheep was evaluated following intravenous (IV) and oral administration of sodium salicylate (sodium salt of salicylic acid) at different doses. Six healthy sheep were administered sodium salicylate (SS) IV at doses of 10, 50, 100 and 200 mg/kg body weight and another six sheep were drenched with 100 and 200 mg/kg of SS orally. Both studies were randomised crossover trials. A one-week washout period between each treatment was allowed in both studies. Blood samples were collected at 0, 15, 30 min and 1, 2, 4 and 6 h after IV and oral SS administrations. Plasma SA concentrations were determined using high-performance liquid chromatography (HPLC) with diode array detection method. Pharmacokinetic variables were calculated in a non-compartmental model. The elimination half-life (T1/2 el) of SA after IV administration of 200 mg/kg SS was 1.16 ± 0.32 h. Mean bioavailability of SA was 64%, and mean T1/2 el was 1.90 ± 0.35 h, after 200 mg/kg of oral SS. The minimum plasma SA concentration (16.8 µg/mL) reported to produce analgesia in humans was achieved after IV administration of 100 and 200 mg/kg SS in sheep for about 0.17 h in this study. Experiments on pharmacokinetic–pharmacodynamics modelling are required to determine the actual effective plasma concentration range of SA in sheep.