Flunixin pharmacokinetics and serum thromboxane inhibition in the dog

McKellar, Quintin; Galbraith, E. A.; Bogan, J. A.; Russell, C.S.; Hooke, R.E.; Lees, P.

doi:10.1136/vr.124.25.651

Cited by 29 publications

(13 citation statements)

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“…The presence of blood in faeces in this study is also in accordance with other reports (McKellar et al 1989;D o w et al 1990). This is a normal finding for dogs not receiving any medication (McKellar et al 1989;McKellar et al 1991b).…”

Section: Discussionsupporting

confidence: 82%

“…This is a normal finding for dogs not receiving any medication (McKellar et al 1989;McKellar et al 1991b). However, the presence of the occult blood was a consistent finding after the 3rd and the 4th day of experiment in group I and II respectively.…”

Section: Discussionmentioning

confidence: 95%

“…These findings are in agreement with the side effects reported for flunixin and NSAIDs at large (M c K ellar et al 1991a; Lees et al 2000). Flunixin inhibits thromboxane A 2 , a potent stimulator of platelet aggregation and vascular smooth muscle contraction, essential components of coagulation, resulting in increased bleeding and coagulation time (McKellar et al 1989;M c K ellar et al 1991b;Lees et al 2000). Another reason for this is thrombocytopenia (Willard et al 1989) that was also the case in this study.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Prolonged Intravenous Flunixin Meglumine in Healthy Dogs

Erdoğan¹,

Güneş²,

Gokce³

et al. 2003

Acta Vet. Brno

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This study was designed to evaluate possible side effects on liver and kidney functions and haematological indices, associated with long-term intravenous (IV) administration of flunixin meglumine in healthy dogs. For this purpose, 12 dogs were divided into 2 equal groups. Group I was intravenously given flunixin meglumine at the dose of 1.1 mg/kg/day for 5 days and group II received 2.2 mg/kg/day IV for 5 days. Blood samples were withdrawn before treatment (day 0), 2 h post injection on each day of treatment and one day after the last injection for biochemical (glucose, sodium-Na, potassium-K, chloride-Cl, creatinine, urea, alkaline phosphatase-AP, alanine amino transferase-ALT and total protein) and haematological (bleeding time, coagulation time, red blood cell, white blood cell, platelet count, differential leukocyte count, haematocrit and haemoglobin) analyses. Faecal and urine samples were collected on the same days as blood samples for the presence of any abnormalities. The results revealed a significant increase in bleeding (P < 0.001) and coagulation time (P < 0.001) and a decrease in platelet count (P < 0.001) in both groups. There was also a significant increase in the concentration of Na and Cl in group I and an elevation in AP (P < 0.001), ALT (P < 0.001) and glucose (P < 0.001) in group II. Blood in urine and faeces was also evident in both groups. The results may suggest that the dose of 1.1 mg/kg IV for 5 d does not cause any significant side effects provided that no bleeding disorder exists, and the dose of 2.2 mg/kg IV for 5 d should not exceed 3 d as liver enzymes began to increase significantly afterwards.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Effects of Prolonged Intravenous Flunixin Meglumine in Healthy Dogs

Erdoğan¹,

Güneş²,

Gokce³

et al. 2003

Acta Vet. Brno

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“…Many evidences show that fever induced by LPS is mediated by a number of endogenous pyrogenic cytokines produced [4,21,22,27]. These pyrogenic cytokines are transported to the thermoregulatory center in the preoptic area, and they stimulate the production of COX-2-dependent prostaglandin (PG) E2, the putative final mediator of the febrile response [15]. The present study demonstrated that LPS caused hyperthermia in both young and adult cats, and that flunixin suppressed dose-dependently hyperthermia induced by LPS.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic and Adverse Effects of Flunixin-Meglumine in Adult and Young Cats

Takata

Hikasa

Satoh

2011

The Journal of Veterinary Medical Science

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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 g/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.KEY WORDS: flunixin-megulumine, gastrointestinal effect, lipopolysaccharide, nonsteroidal anti-inflammatory drug, pharmacokinetics.J. Vet. Med. Sci. 73(12): 1591-1596, 2011 Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used analgesics in veterinary and human medicine. In most species, they are very effective in acute and chronic pains. For example, NSAIDs are often the first drugs used for treatment of pain caused by osteoarthritis in veterinary medicine [20]. In the analgesic study of cats, the effect of flunixin-meglumine (FNX) has been reported in 40 cats undergoing a variety of surgical procedures [9]. It is also well known that NSAIDs cause some adverse effects such as gastrointestinal side-effects in the veterinary medicine. In rats, many kind of NSAIDs have been reported to cause gastrointestinal lesions because of the inhibition of prostaglandins synthesis even new NSAIDs [1]. However, the data on the usage of NSAIDs in cats are less complete than in dogs and, to date, there are no published data about gastrointestinal side-effects in cats.Most NSAIDs are cleared from the body through hepatic metabolism comprising primarily glucuronidation followed by excretion of the resultant polar metabolites via bile and/ or urine. Flunixin is well absorbed from the gastrointestinal tract and undergoes enterohepatic circulation, resulting in a bioavailability of >100% in dogs and cats [16]. At least, two other active transport pathways are invol...

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“…There have been a number of previous studies of the pharmacokinetics of flunixin in dogs. Plasma pharmacokinetics have been reported by Hardie, Hardee, and Rawlings () for up to 12 hr after IV administration and by McKellar et al () and Ogino, Mizuno, Ogata, and Takahashi () for 24 hr after oral and subcutaneous administration, respectively. The range of levels of detection was 10–50 ng/ml in these studies.…”

Section: Introductionmentioning

confidence: 83%

Plasma and urine pharmacokinetics of intravenously administered flunixin in greyhound dogs

Morris

Paine

Zahra

et al. 2019

Vet Pharm & Therapeutics

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Medication control in greyhound racing requires information from administration studies that measure drug levels in the urine as well as plasma, with time points that extend into the terminal phase of excretion. To characterize the plasma and the urinary pharmacokinetics of flunixin and enable regulatory advice for greyhound racing in respect of both medication and residue control limits, flunixin meglumine was administered intravenously on one occasion to six different greyhounds at the label dose of 1 mg/kg and the levels of flunixin were measured in plasma for up to 96 hr and in urine for up to 120 hr. Using the standard methodology for medication control, the irrelevant plasma concentration was determined as 1 ng/ml and the irrelevant urine concentration was determined as 30 ng/ml. This information can be used by regulators to determine a screening limit, detection time and a residue limit. The greyhounds with the highest average urine pH had far greater flunixin exposure compared with the greyhounds that had the lowest. This is entirely consistent with the extent of ionization predicted by the Henderson–Hasselbalch equation. This variability in the urine pharmacokinetics reduces with time, and at 72 hr postadministration, in the terminal phase, the variability in urine and plasma flunixin concentrations are similar and should not affect medication control.

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Flunixin pharmacokinetics and serum thromboxane inhibition in the dog

Cited by 29 publications

References 0 publications

Effects of Prolonged Intravenous Flunixin Meglumine in Healthy Dogs

Effects of Prolonged Intravenous Flunixin Meglumine in Healthy Dogs

Therapeutic and Adverse Effects of Flunixin-Meglumine in Adult and Young Cats

Plasma and urine pharmacokinetics of intravenously administered flunixin in greyhound dogs

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