Interpretation of Changes in Drug Disposition and Interspecies Scaling

Baggot, J. D.

doi:10.1002/9780470690567.ch3

The Physiological Basis of Veterinary Clinical Pharmacology 2001

DOI: 10.1002/9780470690567.ch3

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Interpretation of Changes in Drug Disposition and Interspecies Scaling

J. D. Baggot¹

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Cited by 4 publications

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Plasma and tissue disposition of florfenicol inEscherichia colilipopolysaccharide-induced endotoxaemic sheep

et al. 2016

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1. The purpose of this study was to understand the effects of the acute inflammatory response (AIR) induced by Escherichia coli lipopolysaccharide (LPS) on florfenicol (FFC) and FFC-amine (FFC-a) plasma and tissue concentrations. 2. Ten Suffolk Down sheep, 60.5 ± 4.7 kg, were distributed into two experimental groups: group 1 (LPS) treated with three intravenous doses of 1 μg/kg bw of LPS at 24, 16, and 0.75 h (45 min) before FFC treatment; group 2 (Control) was treated with saline solution (SS) in parallel to group 1. An IM dose of 20 mg FFC/kg was administered at 0.75 h after the last injection of LPS or SS. Blood and tissue samples were taken after FFC administration. 3. The plasma AUC values of FFC were higher (p = 0.0313) in sheep treated with LPS (21.8 ± 2.0 μg·min/mL) compared with the control group (12.8 ± 2.3 μg·min/mL). Lipopolysaccharide injections increased FFC concentrations in kidneys, spleen, and brain. Low levels of plasma FFC-a were observed in control sheep (C = 0.14 ± 0.01 μg/mL) with a metabolite ratio (MR) of 4.0 ± 0.87%. While in the LPS group, C increased slightly (0.25 ± 0.01 μg/mL), and MR decreased to 2.8 ± 0.17%. 4. The changes observed in the plasma and tissue concentrations of FFC were attributed to the pathophysiological effects of LPS on renal hemodynamics that modified tissue distribution and reduced elimination of the drug.

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Plasma and tissue disposition of florfenicol inEscherichia colilipopolysaccharide-induced endotoxaemic sheep

et al. 2016

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In vitro binding of cefovecin to plasma proteins in Australian marsupials and plasma concentrations of cefovecin following single subcutaneous administration to koalas (Phascolarctos cinereus)

2019

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Background Cefovecin has a long duration of antibiotic activity in cats and dogs, somewhat attributable to its high plasma protein binding. Aims To determine the cefovecin binding to plasma proteins in vitro in selected Australian marsupials and to quantify the change in cetovecin concentration over time following subcutaneous injection in koalas. Methods and results Various cefovecin concentrations were incubated with plasma and quantified using HPLC. The median (range) bound percentages when 10 μg/mL of cefovecin was incubated with plasma were 11.1 (4.1–20.4) in the plasma of the Tasmanian devil, 12.7 (5.8–17.3) in the koala, 18.9 (14.6–38.0) in the eastern grey kangaroo, 16.9 (15.7–30.2) in the common brush‐tailed possum, 37.6 (25.3–42.3) in the eastern ring‐tailed possum and 36.4 (35.0–38.3) in the red kangaroo, suggesting that cefovecin may have a shorter duration of action in these species than in cats and dogs. Cefovecin binding to plasma proteins in thawed, frozen equine plasma was also undertaken for assay quality control and the median (range) plasma protein binding (at 10 μg/mL) was 95.6% (94.9–96.6%). Cefovecin was also administered to six koalas at 8 mg/kg subcutaneously and serial blood samples were collected at 3, 6, 24, 48, 72, 96 h thereafter. Cefovecin plasma concentrations were not quantifiable in four koalas and in the other two, the mean plasma concentration at t = 3 h was 1.04 ± 0.01 μg/mL. Conclusion Because of the limited pharmacokinetic data generated, no further pharmacokinetic analysis was performed; however, a single injected bolus of cefovecin is likely to have a short duration of action in koalas (hours, rather than days).

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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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Interpretation of Changes in Drug Disposition and Interspecies Scaling

Cited by 4 publications

References 70 publications

Plasma and tissue disposition of florfenicol inEscherichia colilipopolysaccharide-induced endotoxaemic sheep

Plasma and tissue disposition of florfenicol inEscherichia colilipopolysaccharide-induced endotoxaemic sheep

In vitro binding of cefovecin to plasma proteins in Australian marsupials and plasma concentrations of cefovecin following single subcutaneous administration to koalas (Phascolarctos cinereus)

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

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