Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep

The pharmacokinetics of diclofenac was investigated in sheep given diclofenac alone (1 mg kg(-1), i.v. or i.m.) and in combination with enrofloxacin (5 mg kg-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(1/2 beta)), area under concentration-time-curve (AUC), volume of distribution (Vd(area)), mean residence time (MRT) and total body clearance (013) were 1.03 +/- 0.18 h, 12.17 +/- 1.98 mu g h ml(-1), 0.14 +/- 0.02 L kg(-1), 1.36 +/- 0.16 h and 0.10 +/- 0.02 L kg(-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(1/2 beta), AUC, Vd(area), MRT and Cl-B were 1.33 +/- 0.10h, 7.32 +/- 1.01 mu g h mL(-1), 0.13 +/- 0.01 L kg(-1) and 0.07 +/- 0.0 1 L kg(-1) h(-1), respectively. Co-administration of enrofloxacin did not affect Vd(area) and MRT but absorption rate constant (K-a), beta, t(1/2Ka), t(1/2 beta), 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 1.4 mg kg(-1) of diclofenac administered every 6 h may be appropriate for use in sheep. (c) 2007 Elsevier Ltd. All rights reserved.