Pharmacokinetics and elimination of salicylic acid in rabbits

Abstract

Sodium salicylate was administered to rabbits in order to compare its disposition with that in other major and minor agricultural species. A dose of 44 mg/kg was given orally (p.o.) or intravenously (i.v.), and plasma and urine samples were collected for 36 h and 96 h, respectively. The majority of the drug was excreted as salicylic acid (SA) within 12 h. The major metabolites following an oral dose were salicyluric acid (SUA) and the glucuronide conjugates of SA and SUA. Following i.v. dosing, sulfate conjugates of both SA and SUA were also evident. Both SA and SUA were detected in plasma. Following i.v. administration, SA was distributed with a Vss of 0.249 +/- 0.082 l/kg and cleared at a rate of 0.0432 +/- 0.006 l/h/kg. The biological half-life, calculated from the terminal disposition-rate constant, was 4.3 h (i.v.) or 9.7 h (p.o.). The urinary elimination pattern of SA and metabolites in the rabbit was similar to that previously reported by our laboratories for cattle and goats, although total recovery of the administered dose was not as high as for the latter two species. However, the volume of distribution was larger than for cattle and goats, and rabbits cleared the drug more slowly than those species. As a consequence, the biological half-life was eight to ten times longer than in the ruminants studied previously.

Analytical determination and pharmacokinetics of major metabolites of carbasalate calcium in broilers following oral administration

“…A significant species difference was found in pharmacokinetic parameters for SA. Comparing the results, the t 1 ⁄ 2kz (23.7 h) of SA was different from values reported in chicken (3.13 h), pigeon (14.93 h), duck (5.41 h), turkey (2.99 h), ostrich (1.32 h) (Baert & Backer, 2003), broiler chicken (4.04 h) , rabbit (4.29 h) (Short et al, 1990b), dog (4.49 h) (Waters et al, 1993), cattle (0.48 h) (Short et al, 1990a) and goat (0.50 h) (Short et al, 1990a). The terminal half-life of SA after oral administration of carbasalate calcium was much longer than the terminal half-life in broiler chicken (4.04 h) after intravenous administration of sodium salicylate .…”

“…A significant species difference was found in pharmacokinetic parameters for SA. Comparing the results, the t 1/2λz (23.7 h) of SA was different from values reported in chicken (3.13 h), pigeon (14.93 h), duck (5.41 h), turkey (2.99 h), ostrich (1.32 h) (Baert & Backer, 2003), broiler chicken (4.04 h) (Baert & Backer, 2002), rabbit (4.29 h) (Short et al. , 1990b), dog (4.49 h) (Waters et al.…”

“…, 1984; Baert & Backer, 2003). SU was the major metabolite observed in most species (man, horse, cattle, goat and rat), whereas minor metabolites were detected in rabbits (Short et al. , 1990b) and was not detected in ostriches plasma (Baert et al.…”

Safety Assessment of Salicylic Acid, Butyloctyl Salicylate, Calcium Salicylate, C12–15 Alkyl Salicylate, Capryloyl Salicylic Acid, Hexyldodecyl Salicylate, Isocetyl Salicylate, Isodecyl Salicylate, Magnesium Salicylate, MEA-Salicylate, Ethylhexyl Salicylate, Potassium Salicylate, Methyl Salicylate, Myristyl Salicylate, Sodium Salicylate, TEA-Salicylate, and Tridecyl Salicylate

“…To study the pharmacokinetics and excretion of Sodium Salicylate, four New Zealand white rabbits were given a single oral dose of 44 mg/kg Sodium Salicylate, and blood samples and urine were collected at various intervals for 36 and 96 h, respectively (Short et al 1991). Plasma protein binding of Salicylic Acid was determined by adding radioactive Salicylic Acid to plasma to give final concentrations of 5, 50, and 500 µg/ml.…”

Combining Aspirin with Cholecalciferol (Vitamin D3) – A Potential New Tool for Controlling Possum Populations

“…It has been suggested that cholecalciferol could be combined with anticoagulant pesticides such as diphacinone or coumatetralyl in order to reduce the concentration of these persistent compounds and the consequent hazard to wildlife presented by bioaccumulation [16]. However, aspirin is unlikely to present such a hazard as it is rapidly metabolised and excreted in mammals: for example, in humans seven oral doses of 1 g at six hourly intervals were cleared in less than 48 h [17], and oral doses of 44 mg kg −1 were more than 90% eliminated from goats and cattle in 24 h, and in 12 h from rabbits [18]. While no previous investigations of aspirin with cholecalciferol as a pesticide were located in the scientific literature, one lapsed patent (Patent number 0392934/EP-B1) was found that proposed the combination for more effective rodent control.…”