Pharmacokinetics, tolerance and serum thromboxane inhibition of carprofen in the dog

Abstract

The non-steroidal anti-inflammatory drug (NSAID) carprofen was administered to dogs as a mixed-micelle solution at a dose rate of 0???7 mg/kg intravenously, as a palatable paste at a dose rate of 0???7 mg/kg orally, and as an oral tablet formulation at a dose rate of 0???7 mg/kg and 4-0 mg/kg orally for pharmacokinetic studies. It was also administered as an oral tablet formulation at a dose rate of 9-0 mg/kg orally daily for 14 days in a tolerance study. The pharmacokinetics following intravenous administration at a dose rate of 0???7 mg/kg indicate that carprofen has a small volume of distribution (Vd area = 0???09-0-25 litres), a slow systemic clearance (Cls = 1???34-5-57 ml/min) and an elimination half-life of 3???20-11-77 hours. Both oral paste and tablet preparations were highly bioavailable and absorption was proportional to dose rate at 0???7 mg/kg and 4-0 mg/kg bodyweight. Given once daily at dose rates likely to be used clinically it is unlikely to accumulate in the plasma. Carprofen administered as a palatable paste at a dose rate of 0???7 mg/kg did not inhibit serum thromboxane generation and this drug may therefore have a mode of action different from most NSAIDs. Carprofen was well tolerated when administered as an oral tablet formulation at a dose rate of 9.0 mg/kg daily for 14 days in healthy beagle do

Effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing surgery for fracture repair

“…17 Preoperative use of NSAIDs may increase the incidence of hemorrhage during the perioperative period. 18 However, carprofen does not influence buccal mucosal bleeding time, clotting time, or thromboxane generation by platelets, 9,19 nor does it cause clinically important alterations in hemostatic variables when administered for 5 days. 20 Patients with fractures are considered to have moderate to severe pain.…”

Effects of carprofen or meloxicam on selected haemostatic variables in miniature pigs after orthopaedic surgery

“…Our results correspond with their study, as we also did not find any change of this parameter in pigs after administration of carprofen or meloxicam. Unlike McKellar, we were not able to monitor values of thromboxane B2 as an indicator of COX activity of platelets (McKellar et al 1990(McKellar et al , 1994. We also did not detect significant APTT and PT deviations in control animals after administration of carprofen or meloxicam.…”

“…SAL-0, CAR-0, MEL-0 -pigs before medication, SAL-7, CAR-7, MEL-7 -pigs 7 days after administration of saline, carprofen or meloxicam, TT -thrombin time, U -urea, CR -creatinine Rogers and Levin (1990) desribe buccal mucosal bleeding time as a relatively insensitive screening test. However, McKellar et al (1990) did not observe any change of this parameter after administration of carprofen in dogs. Our results correspond with their study, as we also did not find any change of this parameter in pigs after administration of carprofen or meloxicam.…”

“…Hickford et al (2000) did not observe any clinically significant effects of carprofen on haemostasis in dogs. Buccal mucosal bleeding time and clotting ability (McKellar et al 1990) were not affected by administration of carprofen. McKellar et al (1990McKellar et al ( , 1994 monitored thromboxane B2 as an indicator of COX activity of platelets and found that in vitro administration of carprofen did not impair the platelets' production of thromboxane B2.…”

Exame Gastroscópico Após Administração Oral De Anti-Inflamatórios Não Esteroidais Em Cães

“…Conforme MACPHAIL et al (1998), o carprofeno é o fármaco mais lipofílico da sua classe e seu mecanismo de ação ocorre principalmente através da inibição da fosfolipase A 2 e com pouca ação sobre as cicloxigenases. Devido à sua inibição seletiva COX 2:COX 1, o carprofeno provoca menor toxicose renal e gastrintestinal quando comparado a outras classes de AINES (MCKELLAR et al, 1990;BALMER et al, 1998;MACPHAIL et al, 1998). Segundo VASSEUR et al (1995), as lesões na mucosa gástrica e duodenal são as principais complicações observadas nos cães que recebem carprofeno; estas aparecem com aproximadamente 19 dias após o início do tratamento, mas a prevalência dos efeitos colaterais é baixa em várias espécies, incluindo a humana.…”