Pharmacokinetics and bioavailability of carprofen in sheep

Abstract

The aim of this study was to determine the pharmacokinetics and bioavailability of carprofen in sheep following single intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations of a parenteral formulation at a dose of 4 mg/ kg. A total of eight sheep were used for the investigation. The study comprised four periods, according to a crossover design with a 21-day washout period between treatments. Plasma concentrations of carprofen were measured using HPLC-UV.Pharmacokinetic parameters were estimated by non-compartmental model analysis. Following IV administration, t 1/2ʎz , Cl T , and V dss were 43.36 h, 1.98 ml/h/kg, and 121.36 ml/kg, respectively. The C max(obs) was 26.57 mg/ml for the IM, 23.76 mg/ml for the SC, and 15.90 mg/ml for the PO. The bioavailability following IM, SC, and PO administrations was 75.47%, 82.00%, and 62.51%, respectively. Plasma creatine kinase activity increased significantly at 3, 6, and 12 h following IM administration of carprofen. Despite differences in plasma concentrations and bioavailability among administration routes, carprofen at 4 mg/kg dose may provide the plasma concentration (>1.5 μg/ml) needed for analgesic effect during 144 h in all routes. However, because of the slow absorption rate after SC and PO routes, the IV route may be preferred primarily for the rapid onset in the analgesic and anti-inflammatory effect of carprofen in sheep. Despite the favorable kinetics, the muscle damage caused by IM injection limits use of carprofen via IM route.

Effect of Xylazine on Pharmacokinetics and Physiological Efficacy of Intravenous Carprofen in Castrated Goats Kids

“…The t1/2λz of carprofen in CAST+CRP was found to be 41.59 h, which is consistent with recent findings in sheep (43.36 h) [27] and calves (43.4 h) [35]. Notably, this t1/2λz is longer than that reported for horse, cat, dog, and cows (8.00-30.7 h) [36][37][38][39].…”

“…Carprofen was well tolerated after single and repeated intravenous administration at a dose of 4 mg/kg to sheep [31,32]. It was reported that IV and extravascular (IM, oral, subcutaneous) t 1/2λz of carprofen in sheep were similar and peak plasma concentration was reached in 2.06-11.73 h after extravascular administration [27]. IV administration may be preferred for rapid onset of effect without absorption effect.…”

“…Carprofen concentrations in goat plasma were assayed using the HPLC by modifying the previous published method [26,27]. An amount of 300 µL of acetate buffer (1 M, pH: 2.8) was added to 200 µL of plasma sample and vortexed for 45 s, and then 4 mL of n-butyl acetate was added to this mixture.…”

Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep

“…In our study, the t 1/2ʎz , Cl T and V dss of meloxicam after IV administration at 0.5 mg/kg dose were 10.33 h, 18.76 mL/h/kg and 247.10 mL/ kg, respectively. These data showed that meloxicam was eliminated slowly and had a low volume of distribution, similar to those previously reported in lambs and sheep (t 1/2ʎz , 10.85-14 h; Cl T , 10.20-16.00 mL/h/kg; V d , 180-320 mL/kg, Coskun, Corum, Durna Corum, Cetin, et al, 2023;Shukla et al, 2007;Stock et al, 2013). The low V d of meloxicam may be due to its high plasma protein binding, and ionization at physiological pH.…”

“…The plasma concentrations of meloxicam were assayed by high performance liquid chromatography (HPLC) with ultraviolet detection (UV) using a previous published method (Corum et al., 2022; Coskun, Corum, Durna Corum, & Uney, 2023). A total of 400 μL of methanol (0.1% formic acid) was added to 200 μL of plasma samples.…”