Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep.
The pharmacokinetics of diclofenac was investigated in sheep given diclofenac alone (1mgkg(-1), i.v. or i.m.) and in combination with enrofloxacin (5mgkg(-1), i.v.). The plasma concentration-time data following i.v. administration of diclofenac was best described by a two compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under concentration-time-curve (AUC), volume of distribution (Vd(area)), mean residence time (MRT) and total body clearance (Cl(B)) were 1.03+/-0.18h, 12.17+/-1.98microg h ml(-1), 0.14+/-0.02Lkg(-1), 1.36+/-0.16h and 0.10+/-0.02Lkg(-1)h(-1), respectively. Following i.m. administration of diclofenac alone and in conjunction with enrofloxacin, the plasma concentration-time data best fitted to a one compartment open model. The t(1/2beta), AUC, Vd(area), MRT and Cl(B) were 1.33+/-0.10h, 7.32+/-1.01microg h mL(-1), 0.13+/-0.01Lkg(-1) and 0.07+/-0.01Lkg(-1)h(-1), respectively. Co-administration of enrofloxacin did not affect Vd(area) and MRT but absorption rate constant (K(a)), beta, t1/2Ka, t1/2beta, AUC, AUMC, Cl(B) and bioavailability (F) were significantly increased. This may be due to direct inhibition of cytochrome P(450) isozymes by enrofloxacin. A dose of 1.4mgkg(-1) of diclofenac administered every 6h may be appropriate for use in sheep.
Rahal
Anu
A
Department of Veterinary Pharmacology and Toxicology, College of Veterinary and Animal Sciences, G.B.P.U.A.&T., Pantnagar 263145, India. rahalanu72@yahoo.com
Kumar
Amit
A
Ahmad
A H
AH
Malik
J K
JK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D012756:Sheep
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024841:Fluoroquinolones; D004008:Diclofenac; D000077422:Enrofloxacin