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

SIMPLE SUMMARY: Scarcity of non-steroidal anti-inflammatory drugs (NSAID) to minimise the pain in sheep instigated the current study. The aim of this study was to know the pharmacokinetic parameters of salicylic acid in New Zealand sheep after administration of multiple intravenous and oral doses of sodium salicylate (sodium salt of salicylic acid). Results of the study suggest that the half-life of the drug was shorter and clearance was faster after intravenous administration as compared to that of the oral administration. The minimum effective concentration required to produce analgesia in humans (16.8 µL) was achieved in sheep for about 0.17 h in the current study after intravenous administration of 100 and 200 mg/kg body weight of sodium salicylate. However, oral administration of these doses failed to achieve the minimum effective concentration as mentioned above. This study is of significance as it adds valuable information on pharmacokinetics and its variation due to breed, species, age, gender and environmental conditions. As per the authors’ knowledge, this is the only study showing detailed information about absorption, distribution and elimination of salicylic acid in New Zealand Sheep. An intravenous administration of sodium salicylate at 100 and 200 mg/kg dose may produce analgesia in sheep, which requires further investigation using pharmacokinetic–pharmacodynamic (PKPD) integration or modelling techniques. 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 (T(1/2 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 T(1/2 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.