Pharmacokinetics and Pharmacodynamic Effects of Flunixin after Intravenous, Intramuscular and Oral Administration to Dairy Goats

Königsson, K; Törneke, Karolina; Engeland, IV; Odensvik, K.; Kindahl, H

doi:10.1186/1751-0147-44-153

Cited by 53 publications

(25 citation statements)

References 18 publications

(14 reference statements)

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“…It is commonly used as a measure of drug's potency” [32]. No studies have been conducted on FM EC 50 in swine but a study conducted in the horse determined the EC 50 of FM to be between 0.2-0.9 ug/ml [21] determined FM EC 50 in horses using a chemically induced arthritis model and evaluating thromboxane A generation (an index for NSAID therapeutic effect in horses; [33]. Although inter-species extrapolations of EC 50 drug values may not always be accurate, data generated from this chemically induced arthritis model in the horse may be used as an initial starting point to predict the drug concentration required to provide effective analgesia in lame swine.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration

et al. 2013

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BackgroundThe purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121–168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis.ResultsNo adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749–6004 ng/ml) and 946 ng/ml (range: 554–1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%).ConclusionsThe results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route.

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Section: Discussionmentioning

confidence: 99%

“…Pharmacokinetic (PK) parameters for FM have been evaluated in several species including cattle [19], small ruminants [20,21], horses [18], chickens [22], and companion animals [23]. To the authors’ knowledge there have been two peer-reviewed articles published on FM PK in swine [16,24].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration

et al. 2013

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“…The pharmacokinetics of orally administered flunixin has been studied in goats ( Königsson et al, 2003 ), horses ( Pellegrini-Masini, Poppenga & Sweeney, 2004 ; Welsh et al, 1992 ) and cattle ( Odensvik, 1995 ). Following oral administration of a bolus dose in the absence of feed in these species, flunixin is absorbed rapidly and concentrations can still be detected up to 30 h after administration ( Königsson et al, 2003 ; Odensvik, 1995 ). Horses that had ad libitum access to hay following the oral administration of flunixin had a slower absorption of flunixin and a lower Cmax although concentrations of flunixin in plasma were maintained for longer when animals had access to feed compared with when they were fasted ( Welsh et al, 1992 ).…”

Section: Discussionmentioning

confidence: 99%

Palatability and pharmacokinetics of flunixin when administered to sheep through feed

Marini

Pippia²,

Colditz

et al. 2016

PeerJ

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Applying analgesics to feed is a potentially easy method of providing pain-relief to sheep and lambs that undergo painful husbandry procedures. To be effective, the medicated feed needs to be readily accepted by sheep and its consumption needs to result in therapeutic concentrations of the drug. In the present experiment, pelleted feed was supplemented with flunixin (4.0 mg/kg live weight) and offered to eight sheep. To test the palatability of flunixin, the individually penned sheep were offered normal feed and feed supplemented with flunixin in separate troughs for two consecutive days. A trend for a day by feed-type (control versus flunixin supplemented) interaction suggested that sheep may have had an initial mild aversion to pellets supplemented with flunixin on the first day of exposure, however, by on the second day there was no difference in consumption of normal feed and feed supplemented with flunixin. To test pharmacokinetics, sheep were offered 800 g of flunixin supplemented feed for a 12 h period. Blood samples were taken over 48 h and plasma drug concentrations were determined using ultra-high-pressure liquid chromatography, negative electrospray ionisation and tandem mass spectrometry. The mean ± S.D. time required to reach maximum concentration was 6.00 ± 4.14 h and ranged from 1 to 12 h. Average maximum plasma concentration was 1.78 ± 0.48 µg/mL and ranged from 1.61 to 2.80 µg/mL. The average half-life of flunixin was 7.95 ± 0.77 h and there was a mean residence time of 13.62 ± 1.17 h. Free access to flunixin supplemented feed enabled all sheep to obtain inferred therapeutic concentrations of flunixin in plasma within 6 h of starting to consume the feed. Provision of an analgesic in feed may be an alternative practical method for providing pain relief to sheep.

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“…Flunixin meglumine is used for the control of pyrexia associated with swine respiratory disease. Flunixin meglumine inhibits the cyclo-oxygenase enzyme, thereby decreasing prostaglandin synthesis and is hydroxylated in the liver to 5-hydroxy flunixin [ 25 ]. The objective of the study was to determine if gene expression differences exist across breed and sex for animals given flunixin meglumine or fenbendazole for genes previously shown to play a role in drug metabolism, including CYP1A2 , CYP2E1 , CYP3A22 , CYP3A29 , ABCB1 and SULT1A1 .…”

Section: Introductionmentioning

confidence: 99%

Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine

et al. 2015

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Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169) spread across 5 groups were utilized. Sires (n = 15) of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control), flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value <0.007) basal transcript differences were found across breeds for SULT1A1, CYP3A29 and CYP3A22. Across drugs, significant (P-value <0.0038) transcript differences existed between animals given a drug and controls across breeds and sex for ABCB1, PS and CYP1A2. Significant (P <0.0038) transcript differences across breeds were found for CYP2E1 and SULT1A1 for flunixin meglumine and fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin meglumine and fenbendazole and known drug metabolizing genes.

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Pharmacokinetics and Pharmacodynamic Effects of Flunixin after Intravenous, Intramuscular and Oral Administration to Dairy Goats

Cited by 53 publications

References 18 publications

Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration

Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration

Palatability and pharmacokinetics of flunixin when administered to sheep through feed

Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine

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