Pharmacokinetics of enrofloxacin and flunixin meglumine and interactions between both drugs after intravenous co-administration in healthy and endotoxaemic rabbits

Elmas, Muammer; Yazar, Enver; Üney, Kamil; Er, Ayşe; Traş, Bünyamin

doi:10.1016/j.tvjl.2007.05.021

Cited by 23 publications

(19 citation statements)

References 36 publications

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“…Acute endotoxaemia represents an adequate tool for understanding inflammatory processes (Remick & Ward, 2005). LPS in the blood stream causes fever, disseminated intravascular coagulation, oxidative stress, hypotension, multiple organ failure and, in severe cases, septic shock and death (van Miert, 1994;Elmas et al, 2008). Experiments with different animal species have shown that febrile conditions induced by LPS may alter the pharmacokinetic properties of various chemotherapeutic agents compared to healthy animals (van Miert, 1990).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of florfenicol after intravenous administration in Escherichia coli lipopolysaccharide‐induced endotoxaemic sheep

Pérez

Palma

Drápela

et al. 2014

Vet Pharm & Therapeutics

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Experiments in different animal species have shown that febrile conditions, induced by Escherichia coli lipopolysaccharide (LPS), may alter the pharmacokinetic properties of drugs. The objective was to study the effects of a LPS-induced acute-phase response (APR) model on plasma pharmacokinetics of florfenicol (FFC) after its intravenous administration in sheep. Six adult clinically healthy Suffolk Down sheep, 8 months old and 35.5 ± 2.2 kg in body weight (bw), were distributed through a crossover factorial 2 × 2 design, with 4 weeks of washout. Pairs of sheep similar in body weight were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 μg/kg bw of E. coli LPS before FFC treatment. Group 2 (control) was treated with an equivalent volume of saline solution (SS) at similar intervals as LPS. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples (5 mL) were collected before drug administration and at different times between 0.05 and 48.0 h after treatment. FFC plasma concentrations were determined by liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using a Mann-Whitney U-test. The mean values of AUC0-∞ in the endotoxaemic sheep (105.9 ± 14.3 μg·h/mL) were significantly higher (P < 0.05) than values observed in healthy sheep (78.4 ± 5.2 μg·h/mL). The total mean plasma clearance (CLT ) decreased from 257.7 ± 16.9 mL·h/kg in the control group to 198.2 ± 24.1 mL·h/kg in LPS-treated sheep. A significant increase (P < 0.05) in the terminal half-life was observed in the endotoxaemic sheep (16.9 ± 3.8 h) compared to the values observed in healthy sheep (10.4 ± 3.2 h). In conclusion, the APR induced by the intravenous administration of E. coli LPS in sheep produces higher plasma concentrations of FFC due to a decrease in the total body clearance of the drug.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of florfenicol after intravenous administration in Escherichia coli lipopolysaccharide‐induced endotoxaemic sheep

Pérez

Palma

Drápela

et al. 2014

Vet Pharm & Therapeutics

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“…Pulz et al (2002) suggested that flunixin is capable of causing renal ischemia in dogs due to drug interactions with other anesthetics, but there are few studies that evaluate possible adverse effects caused by it in other animals, especially in laboratory animals. Elmas et al (2008) evaluated the pharmacokinetics of flunixin meglumine in healthy and endotoxemic rabbits and observed that this drug can be coadministered for the treatment of endotoxemia in these animals. Liles and Flecknell (1992), Arumugam et al (2003), Martin and Stewart (2003) believe that this drug may be an alternative for the treatment of pain in rodent species.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of the Effects of Meloxicam and Flunixin Meglumine on Renal Function of Wistar Rats

Torres¹,

Silva

Brancher

et al. 2013

AVS

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This study evaluated the renal function of rats subjected to treatment with meloxicam (ME) and flunixin meglumine (FM). Sixty six Wistar rats were divided into three groups (n=22). The control group received physiological solution, while the groups treated with ME and MF received two subcutaneous doses of 2 and 1.1 mg/kg of the medication, respectively. All animals were subjected to the collection 2 ml of blood at the beginning and end of the study to further detect the levels of urea and creatinine. Double-factor ANOVA test was applied on these data using a significance level ≤ 0.05. The conclusion was that the use of both drugs in therapeutic doses caused significant increase in the plasma urea level. The values of the plasma creatinine were considered equivalent between the groups in all periods. Keywords: analgesia; laboratory animals; experimentation animals ANÁLISE COMPARATIVA DO EFEITO DO MELOXICAM E DO FLUNIXIN MEGLUMINE SOBRE A FUNÇÃO RENAL DE RATOS WISTARRESUMO: Avaliou-se a função renal de ratos Wistar submetidos ao tratamento com meloxicam (ME) e flunixin meglumine (FM). Foram utilizados 66 ratos Wistar distribuídos em três grupos (n=22). O grupo controle recebeu solução fisiológica, enquanto os grupos tratados com ME e FM receberam duas doses de 2 e 1,1 mg/Kg, respectivamente, da medicação por via subcutânea. Todos os animais foram submetidos à coleta de 2 mL de sangue no início e ao fim do estudo para posterior detecção dos níveis de uréia e creatinina plasmáticas. A partir destes dados foi feita a aplicação do teste ANOVA-fator duplo. O nível de significância utilizado foi ≤0,05. Conclui-se que o uso de ambos os medicamentos nas dosagens terapêuticas causou aumento significativo na concentração de uréia plasmática, porém a creatinina plasmática permaneceu equivalente em todos os grupos durante o período de estudo. Palavras-chave: analgesia; animais de laboratório; experimentação animal 39

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“…Large mammals, such as rabbits, are often used in physiological studies requiring invasive monitoring. The rabbit endotoxemia model is created by injecting either E. coli organisms or LPS into the marginal ear vein (Elmas et al, 2008). The rabbit endotoxemia model is created by injecting either E. coli organisms or LPS into the marginal ear vein (Elmas et al, 2008).…”

Section: Rabbit Modelmentioning

confidence: 99%

“…The rabbit, along with sheep and chimpanzees are more sensitive to the effects of endotoxin and show an enhanced response to lower doses of LPS than other species (Parker and Watkins, 2001). This model has been used to demonstrate the poor enteric uptake of D-fructose and L-leucine associated with facilitation of LPS activity by protein kinase C and calmodulin (Amador et al, 2007), and the efficacy of simultaneous treatment with a fluorinated quinolone antibiotic and a non-steroidal anti-inflammatory for the treatment of septicemia (Elmas et al, 2008). This model has been used to demonstrate the poor enteric uptake of D-fructose and L-leucine associated with facilitation of LPS activity by protein kinase C and calmodulin (Amador et al, 2007), and the efficacy of simultaneous treatment with a fluorinated quinolone antibiotic and a non-steroidal anti-inflammatory for the treatment of septicemia (Elmas et al, 2008).…”

Section: Rabbit Modelmentioning

confidence: 99%

The Rabbit as an Experimental Model

Burkholder

Linton

Hoyt

et al. 2012

The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents

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Pharmacokinetics of enrofloxacin and flunixin meglumine and interactions between both drugs after intravenous co-administration in healthy and endotoxaemic rabbits

Cited by 23 publications

References 36 publications

Pharmacokinetics of florfenicol after intravenous administration in Escherichia coli lipopolysaccharide‐induced endotoxaemic sheep

Pharmacokinetics of florfenicol after intravenous administration in Escherichia coli lipopolysaccharide‐induced endotoxaemic sheep

Comparative Analysis of the Effects of Meloxicam and Flunixin Meglumine on Renal Function of Wistar Rats

The Rabbit as an Experimental Model

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