High-performance liquid chromatography method for determination of fhinixin in bovine plasma and pharmacokinetics after single and repeated doses of the drug

Kristina Odensvik From the Department of Obstetrics and Gynaecology, Faculty of Veterinary Medicine, Swedish Uniyersity of Agricultural Sciences, Box 7039, S-750 07 Uppsala (Odensvik), and Medical Products Agency, Box 26, S-751 03 Uppsala (Johansson), Sweden.

Search for other papers by Kristina Odensvik in
Current site
Google Scholar
PubMed
Close
 MSc Pharm
and
I. Monika Johansson From the Department of Obstetrics and Gynaecology, Faculty of Veterinary Medicine, Swedish Uniyersity of Agricultural Sciences, Box 7039, S-750 07 Uppsala (Odensvik), and Medical Products Agency, Box 26, S-751 03 Uppsala (Johansson), Sweden.

Search for other papers by I. Monika Johansson in
Current site
Google Scholar
PubMed
Close
 MSc Pharm, PhD

Click on author name to view affiliation information

SUMMARY

A high-performance liquid chromatography method was developed for determination of flunixin in bovine plasma. The extraction procedure was easily performed and made it possible to detect low concentrations of flunixin with high accuracy. The limit of quantitation was 7 ng/ml (relative standard deviation = 18%, n = 10). The analytic method permits processing of 60 samples/d. Flunixin, as well as the internal standard (diclofenac sodium), belong to the group of nonsteroidal anti-inflammatory drugs, which are known to have a high degree of binding to plasma proteins. Therefore, an evaluation of several buffer systems was undertaken to optimize analytic conditions.

Cattle were given 2.2 mg of flunixin meglumine/kg of body weight. In experiment 1, single injections were administered IV to 1 cow and IV and IM to 1 heifer (7 days apart), and pharmacokinetic variables were calculated. The IV data were best described by a two-compartment model. The half-life after single IV or IM administration was around 4.0 hours. In experiment 2, the decreasing flunixin concentration was determined after the last of either 4 IM injections daily (n = 3 cows) or 2 IM injections daily (n = 3 cows) administered during a 14-day postpartum period. The half-life, determined between 48 and 96 hours after the last dose, was approximately 26 hours in both groups, and flunixin could be detected in plasma up to 8 days, on average.

The protein binding of flunixin was studied, using the method of equilibrium dialysis. Flunixin was found to have a high degree of protein binding (ie, 99.4 ± 0.2%) at a flunixin concentration in plasma of 3 to 24 μg/ml. Differences in protein binding between cattle were not found.

SUMMARY

A high-performance liquid chromatography method was developed for determination of flunixin in bovine plasma. The extraction procedure was easily performed and made it possible to detect low concentrations of flunixin with high accuracy. The limit of quantitation was 7 ng/ml (relative standard deviation = 18%, n = 10). The analytic method permits processing of 60 samples/d. Flunixin, as well as the internal standard (diclofenac sodium), belong to the group of nonsteroidal anti-inflammatory drugs, which are known to have a high degree of binding to plasma proteins. Therefore, an evaluation of several buffer systems was undertaken to optimize analytic conditions.

Cattle were given 2.2 mg of flunixin meglumine/kg of body weight. In experiment 1, single injections were administered IV to 1 cow and IV and IM to 1 heifer (7 days apart), and pharmacokinetic variables were calculated. The IV data were best described by a two-compartment model. The half-life after single IV or IM administration was around 4.0 hours. In experiment 2, the decreasing flunixin concentration was determined after the last of either 4 IM injections daily (n = 3 cows) or 2 IM injections daily (n = 3 cows) administered during a 14-day postpartum period. The half-life, determined between 48 and 96 hours after the last dose, was approximately 26 hours in both groups, and flunixin could be detected in plasma up to 8 days, on average.

The protein binding of flunixin was studied, using the method of equilibrium dialysis. Flunixin was found to have a high degree of protein binding (ie, 99.4 ± 0.2%) at a flunixin concentration in plasma of 3 to 24 μg/ml. Differences in protein binding between cattle were not found.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 53 53 16
PDF Downloads 39 39 3
Advertisement