Gas chromatographic analysis of flunixin in equine urine after extractive methylation

Johansson, Monika; Anlér, Eva-Lotta

doi:10.1016/0378-4347(88)80104-x

Cited by 20 publications

(8 citation statements)

References 6 publications

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“…2). It is unlikely that this peak resulted from ion trapping in the rumen because flunixin is a weak acid with a pKa of 5.82 (Johansson & Anler, 1988) and the pH of the rumen was acidic in nature as measured in this study (5.75 ± 0.07). Similar peaks were also observed previously in human beings and in cattle (Odensvik et al ., 1995) and were attributed to enterohepatic recycling.…”

Section: Discussionmentioning

confidence: 64%

Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels

Wasfi¹,

Boni²,

Hadi³

et al. 1998

Vet Pharm & Therapeutics

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The pharmacokinetics of flunixin were determined after an intravenous dose of 1.1 mg/kg body weight in six camels and 2.2 mg/kg body weight in four camels. The data obtained (mean ± SEM) for the low and high dose, respectively, were as follows: The elimination half‐lives (t½β) were 3.76 ± 0.24 and 4.08 ± 0.49 h, the steady state volumes of distribution (Vdss) were 320.61 ± 38.53 and 348.84 ± 35.36 mL/kg body weight, total body clearances (ClT) were 88.96 ± 6.63 and 84.86 ± 4.95 mL/h/kg body weight and renal clearances (Clr) were 0.52 ± 0.09 and 0.62 ± 0.18 mL/h/kg body weight. A hydroxylated metabolite of flunixin was identified by gas chromatography/mass spectrometry (GC/MS) under electron and chemical ionization and its major fragmentation pattern was verified by tandem mass spectrometry (GC/MS/MS) using neutral loss, daughter and parent scan modes. The detection times for flunixin and its hydroxylated metabolite in urine after an intravenous (i.v.) dose of 2.2 mg/kg body weight were 96 and 48 h, respectively.

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Section: Discussionmentioning

confidence: 64%

Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels

Wasfi¹,

Boni²,

Hadi³

et al. 1998

Vet Pharm & Therapeutics

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“…Exceptions: IMI and β-HBCD carbon labels are unknown. b SAs were adjusted depending on dose, as indicated. Values in parentheses are nominal concentrations for initial fortification. c Average log P calculated from literature log P values accessed from , , , and pubchem.ncbi.nlm.nih.gov/ on 7/14/2017 using the predicted and experimental values were available. d Values for log D at pH 6.8 were calculated using log P values from above sources and p K a ’s from , , , pubchem.ncbi.nlm.nih.gov/, Johansson and Anlér accessed on 7/14/2017. …”

Section: Resultsmentioning

confidence: 99%

Distribution of Chemical Residues among Fat, Skim, Curd, Whey, and Protein Fractions in Fortified, Pasteurized Milk

et al. 2018

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The distribution of 12 environmental contaminants or metabolites with diverse polarities (2,2′,4,4′,5-pentabromodiphenyl ether; bisphenol A; estrone; glyphosate; β-hexabromocyclododecane; imidacloprid; 2,3′,4,4′,5-pentachlorobiphenyl; 3′-methylsulfone 2,2′,4,5,5′-pentachlorobiphenyl; 1,2,7,8-tetrachlorodibenzo- p -dioxin; 2-hydroxy-1,3,7,8-tetrachlorodibenzo- p -dioxin; tetrabromobisphenol A; and triclocarban) among skim milk, fat, curd, whey, whey retentate, and whey permeate was characterized. Analysis of these compounds along with 15 drugs previously studied provided a robust linear model predicting the distribution between skim and fat and the chemical’s lipophilicity (log P , r 2 = 0.71; log D , r 2 = 0.79). Similarly, distribution between curd and whey was correlated with lipophilicity (log P , r 2 = 0.63; log D , r 2 = 0.73). Phenolic compounds had less predictable distribution patterns based on their lipophilicities. Within the whey fraction, chemicals with greater lipophilicity are associated with whey proteins more than hydrophilic chemicals. The resultant model could help predict the potential distribution of chemical contaminants among milk products in cow milk, if present.

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“…The oral absorption of flunixin in this model represented the portion of drug that was absorbed by the rumen and abomasum and reached the liver. Flunixin is absorbed by rumen and abomasum as it is a weak acid with a pka of 5.8 (Johansson & Anler, 1988). This oral absorption is different from the oral bioavailability measured as ratio of the areas under the drug concentration-time curve in blood or plasma (AUC) after oral and IV administration because a portion of drug was cleared by liver before they can reach the systemic circulation.…”

Section: Discussionmentioning

confidence: 99%

Use of population pharmacokinetic modeling and Monte Carlo simulation to capture individual animal variability in the prediction of flunixin withdrawal times in cattle

Baynes

Leavens

et al. 2012

Vet Pharm & Therapeutics

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The objective of this study was to develop a population pharmacokinetic (PK) model and predict tissue residues and the withdrawal interval (WDI) of flunixin in cattle. Data were pooled from published PK studies in which flunixin was administered through various dosage regimens to diverse populations of cattle. A set of liver data used to establish the regulatory label withdrawal time (WDT) also were used in this study. Compartmental models with first-order absorption and elimination were fitted to plasma and liver concentrations by a population PK modeling approach. Monte Carlo simulations were performed with the population mean and variabilities of PK parameters to predict liver concentrations of flunixin. The PK of flunixin was described best by a 3-compartment model with an extra liver compartment. The WDI estimated in this study with liver data only was the same as the label WDT. However, a longer WDI was estimated when both plasma and liver data were included in the population PK model. This study questions the use of small groups of healthy animals to determine WDTs for drugs intended for administration to large diverse populations. This may warrant a reevaluation of the current procedure for establishing WDT to prevent violative residues of flunixin.

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Gas chromatographic analysis of flunixin in equine urine after extractive methylation

Cited by 20 publications

References 6 publications

Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels

Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels

Distribution of Chemical Residues among Fat, Skim, Curd, Whey, and Protein Fractions in Fortified, Pasteurized Milk

Use of population pharmacokinetic modeling and Monte Carlo simulation to capture individual animal variability in the prediction of flunixin withdrawal times in cattle

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