Plasma and tissue kinetics of phenylbutazone and naproxen in dogs.
By means of tissue cages in which a sterile inflammation was induced after injection of carrageenan, plasma and tissue kinetics of two NSAIDs were followed. The first one, phenylbutazone, is characterized by a fairly short elimination half-life (3-6 hours) in dogs, whereas the other one, naproxen, has an average half-life of 67 hours in this species. After a single oral dose of 15 mg/kg, phenylbutazone reached concentrations of 13-20 micrograms/ml in the exudate from the tissue cages. Plasma peak concentrations of 49-75 micrograms/ml were reached. Due to a considerably longer half-life in the exudate than in plasma (7.3-18 hours), the concentration in the exudate exceeded that in plasma at about 20 hours. Naproxen (5 mg/kg, orally) showed a parallel decline in plasma and exudate concentrations for more than 200 hours. Continued treatment for one week with phenylbutazone (15 mg/kg, BID) resulted in plasma concentrations with wide fluctuations between doses, but the concentration in the exudate remained at a constant level. After administration of naproxen (5 mg/kg on the first day and then 2 mg/kg once daily), plasma concentrations remained at 40-50 microgram/ml and those in the exudate at 20-30 microgram/ml throughout the treatment period. Both drugs caused a considerable fall of the leukocyte count in the exudate which may be used as an indicator of the anti-inflammatory effect.
Zech
R
R
Department of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Germany.
Scherkl
R
R
Hashem
A
A
Frey
H H
HH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000493:pharmacokinetics*; D002351:Carrageenan / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D004285:Dogs; D005122:Exudates and Transudates / Q000378:metabolism*; D005260:Female; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009288:Naproxen / Q000097:blood / Q000493:pharmacokinetics; D010653:Phenylbutazone / Q000097:blood / Q000493:pharmacokinetics; D011485:Protein Binding
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D002351:Carrageenan; D010653:Phenylbutazone