ABSTRACT OF THE WEEK

The Journal of veterinary medical science/ the Japanese Society of Veterinary Science
Volume 73 | Issue 12 (December 2011)

Therapeutic and adverse effects of flunixin-meglumine in adult and young cats.

J Vet Med Sci. December 2011;73(12):1591-6.

Kenji Takata¹, Yoshiaki Hikasa, Hiroshi Satoh

¹ Laboratory of Veterinary Internal Medicine, Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, 4–101 Koyama-Minami, Tottori 680–8553, Japan. k_takata32vet@yahoo.co.jp

Abstract

In this study, we elucidated the difference in nonsteroidal anti-inflammatory drug sensitivities between young and adult cats on therapeutic and adverse effects. In the prevention of lipopolysaccharide (LPS)-induced hyperthermia using flunixin-meglumine, young (<3 months old) and adult (>12 months old) cats of both sexes were given LPS (0.3 µg/kg, i.v.), and body temperature was measured 24 hr later. Flunixin (1 mg/kg, s.c.) was administered 30 min before the LPS injection. LPS-induced hyperthermia was almost completely inhibited by pre-treatment with flunixin in both adult and young cats. In addition, flunixin showed almost the same antipyretic effects in both young and adult cats. The animals were administered flunixin (1 mg/kg, s.c.) once a day for 3 days, and sacrificed 24 hr later to examine the gastrointestinal mucosal lesions. In adult cats, flunixin caused many severe lesions in the small intestine. In contrast, very few gastrointestinal lesions were produced by flunixin in young cats. In the pharmacokinetics of flunixin, plasma concentrations of flunixin were analysed using a high performance liquid chromatography. There were no significant differences in plasma concentration of flunixin between young and adult cats from 0.5 to 4 hr after the injection. These results demonstrated that NSAIDs could be used more safely in young than in adult cats from the points of gastrointestinal adverse effects. Furthermore, this difference in gastrointestinal lesions between adult and young cats was not related with the plasma concentration of flunixin.

Companion Notes

Report on the therapeutic and adverse effects of flunixin-meglumine in adult and young cats

Study design

- introduction on nonsteroidal anti-inflammatory drug (NSAID) use in cats

- often 1^st line drugs used for osteoarthritis in veterinary medicine

- currently there are no published reports on gastrointestinal side-effects in cats

- most NSAIDs are cleared through hepatic metabolism

- primarily glucuronidation followed by excretion via bile and/or urine

- glucuronidation in cats is reported to be limited

- therefore, side effects may be more severe in cats

- flunixin-meglumine (FNX)

- used in 40 cats undergoing surgery in 1 report

- well absorbed from GI tract and undergoes enterohepatic circulation

- bioavailability > 100% in dogs and cats

- commonly used in horses and dogs in the USA

- in 1 in vitro study

- flunixin had lower COX-2 selectivity than carprofen and meloxicam

- study population: 20 cats

- 10, young < 3-month-old cats of both sexes weighing 0.4-0.9 kg

- 10, adult > 6-month-old cats of both sexes weighing > 3 kg

- procedures:

- therapeutic phase evaluating effect on experimentally induced pyrexia

- cats placed into 5 treatment groups of both young and adult cats

(4 cats in each of the 5 treatment groups)

- physiological saline only, 0.5 ml/kg sc and IV (CONT group)

- LPS group injected with saline before LPS injection

- flunixin-meglumine, sc 0.5 hours before LPS injection, 12 cats

- 0.25 mg/kg (FNX0.25 group)

- 0.5 mg/kg (FNX0.5 group)

- 1 mg/kg (FNX1.0 group)

- lipopolysaccharide (LPS)-induced hyperthermia

- LPS, 0.3 mg/kg IV

- LPS from gram-negative bacteria results in release of cytokines

- in particular endogenous, pyrogenic cytokines

- these reach the thermoregulatory center in preoptic area

- they stimulate COX-2-dependent prostaglandin production

- body temperature measured at 0.5 hr before and the following:

- 0, 0.5, 1, 2, 4, 8 and 24 hours after the LPS injection

- phase evaluating gastrointestinal lesions due to flunixin:

- cats placed into 2 groups of both young and adult cats

- uninjected groups (young and adult cats)

- flunixin-injected groups (young and adult cats)

- flunixin, 1 mg/kg sc sid after morning meal for 3 days

- cats sacrificed with xylazine and sodium pentobarbital

- 24 hours after last flunixin injection

- gastric mucosa examined using stereomicroscopy

- lesion area calculated

- pharmacokinetic analysis

- blood collected at 0, 0.5, 1, 2 and 4 hours after flunixin injection

- plasma analyzed by high performance liquid chromatography

Results

- LPS-induced hyperthermia nearly completely inhibited by pretreatment flunixin

(2 hours after LPS injection alone temperatures peaked at 39.35 ± 0.15°C)

- in both adult and young cats and with nearly same antipyretic effects

- LPS-induced hyperthermia reduced in a dose-dependent manner in adults

- in cats administered 1 mg/kg flunixin sc once a day for 3 days and sacrificed

- adult cats: many, severe small intestinal lesions

- erosion area was 1.52 ± 0.89% of total surface area

- young cats: few GI lesions

- erosion area was 0.09 ± 0.04% of total surface area

- difference between the 2 age groups not related to plasma levels

- flunixin pharmacokinetics

- no significant differences in plasma levels between young and adult cats

- from 0.5 to 4 hours post-injection

- blood levels reached maximum at 0.5 hours after sc injection

- T_max after sc injection: 0.5-1.0 hours

- reported T_max after PO use in cats: 1.3-2 hours

- 1 hour after injection blood levels were at about 50% of maximum

- levels gradually fell after that

“In the present study, as the FNX caused severe gastrointestinal adverse effects in adult cats, it may not be suitable for the use to adult cats. Although the essential causes of the difference are unknown, the present results suggest that NSAIDs could be safer in young than in adult cats, with respect to gastrointestinal adverse effects.”

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