Pharmacokinetic, biochemical and tolerance studies on carprofen in the horse

Abstract

Carprofen, a non-steroidal anti-inflammatory drug (NSAID) was administered to three Thoroughbred geldings and three Shetland ponies to determine its plasma disposition and tolerance. The main pharmacokinetic characteristics of carprofen in horses and ponies were a volume of distribution of 0.08 to 0.32 litres/kg (mean +/- se = 0.23 +/- 0.04) a systemic clearance of 26.4 to 78.5 ml/min (mean +/- se = 44.9 +/- 8.0) and a plasma elimination half-life of 14.5 to 31.4 h (mean +/- se = 21.9 +/- 2.3). There was no evidence of any accumulation of carprofen in plasma when the drug was given orally at a dose rate of 0.7 mg/kg for 14 consecutive days. Carprofen was well tolerated following intravenous (iv) and oral administration. Intramuscular (im) administration resulted in elevated levels of plasma creatine kinase suggesting muscle cell damage. According to the results of this study carprofen can be regarded as a long-acting NSAID in horses from a pharmacokinetic point of view. Either iv, im or the oral route of administration could be used to achieve high carprofen plasma concentrations

A study of the pharmacokinetics and thromboxane inhibitory activity of a single intramuscular dose of carprofen as a means to establish its potential use as an analgesic drug in white rhinoceros

“…Carprofen was characterized by a fairly long absorptive phase with a T max of 9.51 ± 3.53 hr (corresponding C max of 5.77 ± 1.55 μg/ml). The absorptive phase compares favourably with the horse, which exhibits a comparable T max of 10.6 ± 1.6 hr, albeit at a lower maximum concentration of 2.2 ± 0.4 μg/ml following a single dose of 0.7 mg carprofen/kg (McKellar et al., ). While we did not specifically evaluate the reason for the slow absorption of the drug from the site of injection, we believe that it may be attributed to two possible causes.…”

“…This process has been evaluated in the horse, where an increase in creatinine kinase (CK) activity, a marker of muscle cell damage, was noted after i.m. carprofen injection (McKellar et al., ). From pharmacokinetic theory, is it known that localized irritation at the administration site can slow absorption (McKellar et al., ), which is used in formulation chemistry to create long‐lasting effects for certain antibiotic formulations (Xia, Gyrd‐Hansen, & Nielsen, ).…”

“…The half‐life in the white rhino is substantially longer than the 29.4 ± 3 hr following a single i.m. dose at 0.7 mg/kg in the horse (McKellar et al., ); or the 30.7 ± 2.3 hr in the cow (Lohuis et al., ) and 26.1 ± 1.1 hr in sheep (0.7 mg/kg IV; Welsh et al., ). To our knowledge, the half‐life in the white rhinoceros is the longest recorded half‐life amongst all mammalian species.…”

“…as well as subcutaneously (s.c.) and per os (p.o. ;McKellar, Bogan, von Fellenberg, Ludwig, & Cawley, 1991;McKellar, Delatour, & Lees, 1994;Taylor et al, 1996). Carprofen is characterized by a low volume of distribution in steady-state of 0.093 L/kg in sheep (Welsh, Baxter, & Nolan, 1992), 0.14 L/kg in the dog (McKellar et al, 1990) and 0.091 L/kg in the cow (Lohuis et al, 1991).…”

Use of firocoxib for the treatment of equine osteoarthritis

“…74 Anecdotally, carprofen has been used at Colorado State University in horses that developed high serum creatinine levels and diarrhea in association with phenylbutazone use. These side effects disappeared after discontinuation of phenylbutazone with carprofen administration.…”