Preliminary pharmacokinetic and pharmacodynamic studies on flunixin meglumine in donkeys
There are relatively few non-steroidal anti-inflammatory drugs (NSAIDs) for which basic pharmacokinetic and toxicological data are available in the cat. This paper describes some pharmacokinetics and pharmacodynamics of flunixin in this species. Six healthy adult female cats were given 1.0 mg kg-1 flunixin meglumine orally daily for 7 consecutive days. Indwelling catheters were placed on the day preceding the first and last flunixin doses and 2 ml blood samples were taken for flunixin and thromboxane B2 (TXB2) assay before dosing and at 1, 2, 3, 5, 7, and 24 h after the first and the last doses of flunixin. Blood samples for haematology were taken before any treatment had been given and on treatment days 4 and 7 as well as 7 days after the end of treatment. On the first day of dosing, Cmax ranged from 0.45-6.94 micrograms ml-1 flunixin and the mean plasma concentration was greatest at 1 h (2.46 micrograms ml-1). No flunixin was detected by 24 h. After 7 days dosing, Cmax ranged from 0.47-2.46 micrograms ml-1. The mean plasma concentration was again greatest at 1 h but was lower (1.68 micrograms ml-1) than on the first day of treatment. No flunixin was detected beyond 5 h after dosing. The area under the plasma concentration time curve 0-24 h on the first day was 6.82 +/- 1.85 micrograms ml-1h-1 and 3.32 +/- 0.73 micrograms ml-1h-1 on the seventh day. On the first treatment day, serum TXB2 was inhibited by at least 75% in all post-treatment samples up to 7 h but on the seventh day it was reduced only at 1 and 2 h after dosing. Serum TXB2 was significantly higher on the seventh treatment day compared with the first at 3, 5 and 7 h after dosing. No abnormal clinical signs were seen and appetite was unaffected throughout the study. Most biochemical and haematological values remained within normal limits although alanine aminotransferase increased from 11.4-21.3 iu l-1 on day 7 without any other evidence of abnormality. The data suggest that the cats developed tolerance to flunixin although it is not known whether this was due to liver enzyme induction or reduced drug absorption. It is interesting that the cat, despite its reputation for inability to eliminate NSAIDs, has a relatively short flunixin half life and appears to develop tolerance to the drug.