PLASMA AND TISSUE KINETICS OF PHENYLBUTAZONE AND NAPROXEN IN DOGS

By means of tissue cages in which a sterile inflammation was induced a fter injection of carrageenan, plasma and tissue kinetics of two NSAID s were followed. The first one, phenylbutazone, is characterized by a fairly short elimination half-life (3-6 hours) in dogs, whereas the ot her one, naproxen, has an average half-life of 67 hours in this specie s. After a single oral dose of 15 mg/kg, phenylbutazone reached concen trations of 13-20 mug/ml in the exudate from the tissue cages. Plasma peak concentrations of 49-75 mug/ml were reached. Due to a considerabl y longer half-life in the exudate than in plasma (7.3-18 hours), the c oncentration in the exudate exceeded that in plasma at about 20 hours. Naproxen (5 mg/kg, orally) showed a parallel decline in plasma and ex udate concentrations for more than 200 hours. Continued treatment for one week with phenylbutazone (15 mg/kg, BID) resulted in plasma concen trations with wide fluctuations between doses, but the concentration i n the exudate remained at a constant level. After administration of na proxen (5 mg/kg on the first day and then 2 mg/kg once daily), plasma concentrations remained at 40-50 mug/ml and those in the exudate at 20 -30 mug/ml throughout the treatment period. Both drugs caused a consid erable fall of the leukocyte count in the exudate which may be used as an indicator of the anti-inflammatory effect.