Ketoprofen concentrations in plasma and milk after intravenous administration in dairy cattle.
OBJECTIVE
To determine plasma and milk concentration-time profiles and pharmacokinetic variables after i.v. administration of ketoprofen to lactating dairy cows.


METHODS
Cows received a single i.v. 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.


METHODS
6-clinically normal lactating Holstein cows.


METHODS
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 of half-life for ketoprofen is short, and low concentrations of ketoprofen can be detected in normal milk, after i.v. treatment of cattle with ketoprofen. Milk and meat from cattle treated i.v. with ketoprofen should not be an important drug residue risk if appropriate withholding periods are used.
De Graves
F J
FJ
DEpartment of Large Animal Surgery and Medicine, College of Veterinary Medicine, Auburn University, AL 36849-5522, USA.
Riddell
M G
MG
Schumacher
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D007275:Injections, Intravenous; D007660:Ketoprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007774:Lactation; D008892:Milk / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen