Pharmacokinetics of intravenous and subcutaneous cefovecin in alpacas

The purpose of this study was to determine the pharmacokinetics of cefovecin after intravenous and subcutaneous dose of 8 mg/kg to alpacas. Bacterial infections requiring long‐term antibiotic therapy such as neonatal bacteremia, pneumonia, peritonitis, dental, and uterine infections are a significant cause of morbidity and mortality in this species. However, few antimicrobials have been evaluated and proven to have favorable pharmacokinetics for therapeutic use. Most antimicrobials that are currently used require daily injections for many days. Cefovecin is a long‐acting cephalosporin that is formulated for subcutaneous administration, and its long‐elimination half‐life allows for 14‐day dosing intervals in dogs and cats. The properties of cefovecin may be advantageous for medical treatment of camelids due to its broad spectrum, route of administration, and long duration of activity. Pharmacokinetic evaluation of antimicrobial drugs in camelids is essential for the proper treatment and prevention of bacterial disease, and to minimize development of antibiotic resistant bacterial strains due to inadequate antibiotic concentrations. Cefovecin mean half‐life, volume of distribution at steady‐state, and clearance after intravenous administration were 10.3 h, 86 mL/kg, and 7.07 mL·h/kg. The bioavailability was 143%, while half‐life, Cmax, and Tmax were 16.9 h, 108 μg/mL, and 2.8 h following subcutaneous administration. In the absence of additional microbial susceptibility data for alpaca pathogens, the current cefovecin dosage regimen prescribed for dogs (8 mg/kg SC every 14 days) may need to be optimized for the treatment of infections in this species

Phenotypic variations of orpk mutation and chromosomal localization of modifiers influencing kidney phenotype.

The Oak Ridge polycystic kidney (orpk) mutant mouse model resulted from a transgene insertion into the Tg737 gene and exhibits a pleiotropic syndrome with lesions in the kidney, liver, and pancreas. We found marked differences in the phenotypic expression of the orpk mutation when bred on different genetic backgrounds. In the FVB/N background, the phenotype is very severe for kidney, pancreas, and liver lesions. To evaluate better how genetic background might influence the expressivity of the orpk phenotype, we bred the transgene into the C3HeB/FeJLe (C3H) genetic background. We performed a genome-wide scan using backcross and intercross populations with more than 150 markers to map the chromosomal location of the modifier genes that differ in the FVB/N and C3H genetic backgrounds that affect the severity of kidney disease in the orpk mouse. Low-resolution interval mapping was performed using the Map Manager QTb program, with the interval explaining a significant portion of the variance being the distal end of chromosome 4

Efficacy of taxol in the orpk mouse model of polycystic kidney disease.

Polycystic kidney disease (PKD) a is common disease in the human population that can lead to renal failure and death. Taxol has recently been reported to be of therapeutic benefit in the cpk mouse model of PKD. To determine whether these results also apply to other models of PKD, we studied the effects of taxol treatment on the development of renal cysts and biliary hyperplasia/dysplasia/fibrosis in the orpk mouse mutant, a unique murine model for human autosomal recessive PKD. We report no significant differences between the treatment and control groups with respect to weight gain, survival, urine to serum osmolality ratio, and serum concentration of liver enzymes. Moreover, renal cystic development was not affected by taxol treatment in the orpk mutant animals. This was confirmed by lectin staining and morphometric analysis of the renal cysts, which indicated no significant differences between treatment groups. Therefore, while taxol has a positive effect on the cystic kidney disease in cpk mutant mice, this effect is not applicable to all forms of PKD