Ketoprofen concentrations in plasma and milk after intravenous administration in dairy cattle

Abstract

Abstract Objective To determine plasma and milk concentration-time profiles and pharmacokinetic variables after IV administration of ketoprofen to lactating dairy cows. Design Cows received a single IV bolus of ketoprofen (3.31 mg/kg of body weight). Blood and milk were collected at 0, 5, 10, 15, 25, 40, 60, 90, 120, 180, 240, 360, and 480 minutes. Ketoprofen concentrations in plasma and milk were determined. Animals 6 clinically normal lactating Holstein cows. Procedure Plasma and milk samples were processed by solvent extraction, and ketoprofen concentrations were determined, using high-performance liquid chromatography with octadecyl silane reverse-phase guard and analytic columns. A computer polyexponential curve-stripping program was used to fit ketoprofen concentration-time data and to calculate pharmacokinetic variables. Results The lower limit of detection for ketoprofen in plasma was 18 ng/ml; the lower limit of quantification was 60 ng/ml. The lower limit of detection for ketoprofen in milk was 27 ng/ml; the lower limit of quantification was 90 ng/ml. Plasma ketoprofen concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean apparent volume of distribution at steady state was 0.11 (range, 0.095 to 0.13) L/kg, elimination half-life was 0.49 (range, 0.40 to 0.67) hour, and total clearance was 0.17 (range, 0.14 to 0.19) L/kg/h. Ketoprofen was detected in some milk samples, 10 to 120 minutes after administration, but all concentrations were below the limit of quantification. Adverse effects were not observed in cows given ketoprofen. Conclusions The elimination half-life for ketoprofen is short, and low concentrations of ketoprofen can be detected in normal milk, after IV treatment of cattle with ketoprofen. Milk and meat from cattle treated IV with ketoprofen should not be an important drug residue risk if appropriate withholding periods are used. (Am J Vet Res 1996;57:1031–1033)