Pharmacokinetics of carprofen enantiomers in equine plasma and synovial fluid - a comparison with ketoprofen.
Carprofen is a Non Steroidal Anti-Inflammatory Drug (NSAID) which is widely used for the treatment of musculoskeletal disorders in horses. The commercial preparation is a racemic mixture of two enantiomers (R and S carprofen). We used HPLC to measure plasma and synovial fluid R and S carprofen concentrations following a single intravenous (i.v.) dose, and computer modelling to determine the pharmacokinetic parameters of the enantiomers in these two body fluids. A comparison was made with results from an identical experiment using ketoprofen. The plasma elimination half lives of R and S carprofen were 20 and 16 times longer than those of R and S ketoprofen, and clearance was considerably slower for carprofen than ketoprofen. Plasma R carprofen concentrations were higher than S carprofen concentrations throughout the 48-h period. Ketoprofen was no longer detectable in synovial fluid after 5 h (S enantiomer) or 12 h (R enantiomer), whereas synovial fluid carprofen concentrations did not peak until 12 h and were still detectable at 48 h. Synovial fluid concentrations of both carprofen enantiomers were significantly lower than plasma concentrations, probably due to high plasma protein binding which could limit transfer through the synovial membrane. Our results indicate significant differences between carprofen and ketoprofen and between the two carprofen enantiomers.
Armstrong
S
S
The Royal Veterinary College, North Mymms, Hatfield, Hertfordshire, UK.
Tricklebank
P
P
Lake
A
A
Frean
S
S
Lees
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002227:Carbazoles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D007660:Ketoprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D013582:Synovial Fluid / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D007660:Ketoprofen; C007005:carprofen