The Effect of Pasteurella haemolytica A2 Infection on Phagocytosis Efficiency of Caprine Broncho-Alveolar Macrophages

et al. 2011

Physiologically based pharmacokinetic (PBPK) models, which incorporate species- and chemical-specific parameters, could be useful tools for extrapolating withdrawal times for drugs across species and doses. The objective of this research was to develop a PBPK model for goats to simulate the pharmacokinetics of tulathromycin, a macrolide antibiotic effective for treating respiratory infections. Model compartments included plasma, lung, liver, muscle, adipose tissue, kidney, and remaining poorly and richly perfused tissues. Tulathromycin was assumed to be 50% protein bound in plasma with first-order clearance. Literature values were compiled for physiological parameters, partition coefficients were estimated from tissue:plasma ratios of AUC, and the remaining model parameters were estimated by comparison against the experimental data. Three separate model structures were compared with plasma and tissue concentrations of tulathromycin in market age goats administered 2.5 mg/kg tulathromycin subcutaneously. The best simulation was achieved with a diffusion-limited PBPK model and absorption from a two-compartment injection site, which allowed for low persistent concentrations at the injection site and slower depletion in the tissues than the plasma as observed with the experimental data. The model with age-appropriate physiological parameters also predicted plasma concentrations in juvenile goats administered tulathromycin subcutaneously. The developed model and compilation of physiological parameters for goats provide initial tools that can be used as a basis for predicting withdrawal times of drugs in this minor species.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats

Leavens

Tell

et al. 2011

show abstract

“…implicated as the most common bacterial causes (Brogden et al. , 1998; Ackermann & Brogden, 2000; Zamri‐Saad & Mera, 2001; Berge et al. , 2006; Washburn et al.…”

Section: Introductionmentioning

confidence: 99%

Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus)

Leavens

Griffith

et al. 2011

Tulathromycin is a macrolide antimicrobial labeled for treatment of bacterial pneumonia in cattle and swine. The purpose of the present research was to evaluate tissue concentrations of tulathromycin in the caprine species. A tandem mass spectrometry regulatory analytical method that detects the common fragment of tulathromycin in cattle and swine was validated with goat tissues. The method was used to study tulathromycin depletion in goat tissues (liver, kidney, muscle, fat, injection site, and lung) over time. In two different studies, six juvenile and 25 market-age goats received a single injection of 2.5 mg/kg of tulathromycin subcutaneously; in a third study, 18 juvenile goats were treated with 2.5, 7.5, or 12.5 mg/kg tulathromycin weekly with three subcutaneous injections. Mean tulathromycin tissue concentrations were highest at injection site samples in all studies and all doses. Lung tissue concentrations were greatest at day 5 in market-age goats while in the multi-dose animals concentrations demonstrated dose-dependent increases. Concentrations were below limit of quantification in injection site and lung by day 18 and in liver, kidney, muscle, and fat at all time points. This study demonstrated that tissue levels in goats are very similar to those seen in swine and cattle.

show abstract

“…, 2007; Yener et al. , 2009; Zamri‐Saad & Mera, 2001). Options for approved antibiotic therapy to combat bacterial infections in caprines are severely limited and often must be administered in an off‐label manner (Berge et al.…”

Section: Mean Results and Ranges From Clinical Pathology Sample Testmentioning

confidence: 99%

Safety evaluation of tulathromycin use in the caprine species: tulathromycin toxicity assessment in goats

Jordan

Loynachan

et al. 2010