Protein binding and in vitro serum thromboxane B2 inhibition by flunixin meglumine and meclofenamic acid in dog, goat and horse blood

Galbraith, E. A.; McKellar, Quintin

doi:10.1016/s0034-5288(96)90115-0

Cited by 18 publications

(18 citation statements)

References 16 publications

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“…The volumes of distribution were low and similar for both enantiomers for each route of administration, implying a high degree of plasma protein binding (Lees et al. , 1987, 2004b; Galbraith et al. , 1996).…”

Section: Discussionmentioning

confidence: 99%

“…parameters (only AUC 0 fi ¥ and k z were compared). of distribution were low and similar for both enantiomers for each route of administration, implying a high degree of plasma protein binding (Lees et al, 1987(Lees et al, , 2004bGalbraith et al, 1996). High degrees of protein binding can limit glomerular filtration of NSAIDs and thus their excretion in urine, so species differences in CPF clearance when low volumes of distribution are present are often associated with differences in hepatic clearance Lees et al, 2004b).…”

Section: Discussionmentioning

confidence: 99%

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Enantioselective pharmacokinetics of racemic carprofen in New Zealand white rabbits

Hawkins¹,

Taylor²,

Craigmill

et al. 2008

Vet Pharm & Therapeutics

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The enantioselective pharmacokinetics of single dose (2 mg/kg) racemic carprofen (CPF) were evaluated in adult New Zealand white rabbits after intravenous (i.v.) and subcutaneous (s.c.) dose. Six rabbits were utilized in a two-way randomized crossover study and serial blood samples were collected. Plasma CPF concentrations were determined by high-performance liquid chromatography. After i.v. and s.c. racemic CPF administration, plasma concentration-time curves were best described by a two-compartment open model and a one-compartment model, respectively. The S(+) CPF enantiomer predominated in plasma following both routes of administration. Mean observed clearance of R(-)-CPF (82.17 +/- 13.70 mL/h.kg) was more rapid than for S(+)-CPF (27.92 +/- 7.07 mL/h.kg; P < 0.001). T(1/2)lambda z was shorter for R(-)-CPF than S(+)-CPF after both i.v. (1.03 and 2.99 h, respectively) and s.c. (1.94 and 4.14 h, respectively) dosing. Mean AUC(0-->infinity) ratios for R(-):S(+)-CPF were approximately 1:3 for both routes of administration. Mean residence time of R(-)-CPF was shorter than of S(+)-CPF (1.06 +/- 0.29 h, 3.45 +/- 0.50 h; P < 0.001) and R(-)- and S(+)-CPF volumes of distribution at steady state were 85.00 +/- 14.42 and 94.39 +/- 18.66 mL/kg, respectively after i.v. administration. The mean s.c. bioavailability [F (%)] for both R(-)- and S(+)-CPF was high, 94.4 +/- 22.8 and 91.0 +/- 35.7%, respectively.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Enantioselective pharmacokinetics of racemic carprofen in New Zealand white rabbits

Hawkins¹,

Taylor²,

Craigmill

et al. 2008

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

show abstract

“…However, it remains to be determined whether this effect would be significant in vivo or in the face of inflammatory stimuli. Other similar studies have evaluated the efficacy of NSAIDs, including FM, in horses without the induction of inflammation and demonstrated significant inhibition of PGE 2 and/ or TXB 2 (Beretta, Garavaglia, & Cavalli, 2005;Brideau, Van Staden, & Chan, 2001;Galbraith & McKellar, 1996;Jackman et al, 1994;Kim et al, 2015;Knych, Arthur, McKemie, & Chapman, 2015;Lees, Ewins, Taylor, & Sedgwick, 1987;Soma, Uboh, Rudy, & Fegely, 1992). Given that FM is currently considered the standard of care for LPS-induced inflammation in horses, it was important to compare the ability of KT and FM in suppressing LPS-induced eicosanoids with the same experimental conditions applied.…”

Section: Discussionmentioning

confidence: 99%

In vitro anti‐LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses

Bianco

Moore

Cooper

et al. 2017

Vet Pharm & Therapeutics

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Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed.Ketorolac tromethamine and FM suppressed LPS-induced Thromboxane B 2 (TXB 2 ) and Prostaglandin E 2 (PGE 2 ) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS-induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti-inflammatory and analgesic effects of KT is warranted.

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“…23 Although protein binding can limit the passage of a drug from plasma into interstitial fluid, it also facilitates the sequestration of NSAIDs in inflamed tissues because protein readily leaks into those tissues. 29,44 It is likely that inflammation alters the metabolism or disposition of flunixin, which results in a prolonged MRT of flunixin residues in milk and other tissues. 28,42 Detectable flunixin concentrations persisted in milk for up to 60 hours after administration in 3 of 10 cows with clinical mastitis that were treated with 1 (labeled) dose of flunixin in conjunction with parenteral and intramammary administration of antimicrobials (mean ± SD flunixin concentration, 13.02 ± 10.93 ppb), whereas flunixin was detectable in milk for only 24 hours after administration in all 10 like-treated healthy control cows.…”

Section: Effect Of Disease On Wdimentioning

confidence: 99%

Avoiding violative flunixin meglumine residues in cattle and swine

Sidhu

Gehring

Mzyk

et al. 2017

javma

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Protein binding and in vitro serum thromboxane B2 inhibition by flunixin meglumine and meclofenamic acid in dog, goat and horse blood

Cited by 18 publications

References 16 publications

Enantioselective pharmacokinetics of racemic carprofen in New Zealand white rabbits

Enantioselective pharmacokinetics of racemic carprofen in New Zealand white rabbits

In vitro anti‐LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses

Avoiding violative flunixin meglumine residues in cattle and swine

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