Pharmacodynamics and enantioselective pharmacokinetics of carprofen in the cat.
The pharmacodynamics and enantioselective pharmacokinetics of the arylpropionic acid non-steroidal anti-inflammatory drug, carprofen, were investigated in cats after administration of the racemic mixture (rac-carprofen) at dose rates ranging from 0.7 to 4.0 mg kg-1 intravenously and subcutaneously. A low dose of rac-carprofen (0.7 mg kg-1) partially inhibited the rise in skin temperature at a site of acute inflammation but had no effect on the ex vivo synthesis of serum thromboxane (Tx) B2. A higher dose (4.0 mg kg-1) inhibited oedematous swelling, although the response was statistically significant at only one time, and also reduced the ex vivo synthesis of serum TxB2 for 12 hours after intravenous injection or 24 hours after subcutaneous injection. The main features of carprofen pharmacokinetics were a low distribution volume, a relatively long elimination half-life, the predominance of the R(-) enantiomer and a bioavailability (after subcutaneous dosing) of 100 per cent and 92 per cent, respectively, after doses of 0.7 and 4.0 mg kg-1. On the basis of these data, it is suggested that a dose of 4.0 mg kg-1 by both intravenous and subcutaneous routes should be evaluated in clinical subjects.
Taylor
P M
PM
Department of Clinical Veterinary Medicine, University of Cambridge.
Delatour
P
P
Landoni
F M
FM
Deal
C
C
Pickett
C
C
Shojaee Aliabadi
F
F
Foot
R
R
Lees
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002227:Carbazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002415:Cats; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D009919:Orchiectomy; D010052:Ovariectomy; D012867:Skin / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects*; D013237:Stereoisomerism; D013929:Thromboxane B2 / Q000097:blood*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D013929:Thromboxane B2; C007005:carprofen