Pharmacokinetics and pharmacodynamic effects of flunixin after intravenous, intramuscular and oral administration to dairy goats.
The pharmacokinetics and the prostaglandin (PG) synthesis inhibiting effect of flunixin were determined in 6 Norwegian dairy goats. The dose was 2.2 mg/kg body weight administered by intravenous (i.v.). intramuscular (i.m.) and oral (p.o.) routes using a cross-over design. Plasma flunixin content was analysed by use of liquid chromatography and the PG synthesis was evaluated by measuring plasma 15-ketodihydro-PGF2alpha by a radioimmuno-assay. Results are presented as median (range). The elimination half-lives (t(1/2) x lambda) were 3.6 (2.0-5.0), 3.4 (2.6-6.8) and 4.3 (3.4-6.1) h for i.v., i.m. and p.o. administration, respectively. Volume of distribution at steady state (Vd(ss)) was 0.35 (0.23-0.4 1) L/kg and clearance (CL), 110 (60-160) mL/h/kg. The plasma concentrations after oral administration showed a double-peak phenomenon with the two peaks occurring at 0.37 (0.25-1) and 3.5 (2.5-5.0) h, respectively. Both peaks were in the same order of magnitude. Bioavailability was 79 (53-112) and 58 (35%-120)% for i.m. and p.o. administration, respectively. 15-Ketodihydro-PGF2, plasma concentrations decreased after flunixin administration independent of the route of administration.
Königsson
K
K
Department of Obstetrics and Gynaecology, Centre for Reproductive Biology in Uppsala, Uppsala, Sweden.
Törneke
K
K
Engeland
I V
IV
Odensvik
K
K
Kindahl
H
H
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003002:Clonixin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D005260:Female; D006041:Goats; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D011453:Prostaglandins / Q000096:biosynthesis*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; C014557:flunixin; D003002:Clonixin