No abstract

The impact of Escherichia coli-derived lipopolysaccharide (LPS) on the pharmacokinetic parameters of enrofloxacin in swine was assessed to determine whether this model would substitute for a pleuropneumonia infection model for pharmacokinetic evaluation of drugs. All animals received a single i.v. dose of enrofloxacin (5 mg/kg). Half the animals also received dexamethasone (0.5 mg/kg) to determine the impact of inflammation on any changes in enrofloxacin pharmacokinetics, as most of the effects of LPS are due to elaboration of inflammatory mediators. Administration of LPS alone (2.0 microg/kg) was associated with a decrease in clearance of enrofloxacin. Volume of distribution at steady state was increased in the dexamethasone-treated animals. The terminal elimination half-life of enrofloxacin was significantly increased in the LPS group. Dexamethasone administration, either alone or in combination with LPS challenge, increased the volume of distribution both at steady state and during the elimination phase. Lipopolysaccharide challenge did not affect the volume of distribution. Lipopolysaccharide challenge did not affect urinary excretion of enrofloxacin but did increase the urinary excretion of its principal metabolite, ciprofloxacin. However, the increased excretion did not begin until 24 h after administration of enrofloxacin. Because these pharamcokinetic results are different from those obtained with the pleuropneumonia model using the bacteria Actinobacillus pleuropneumoniae, the results of this study demonstrate that LPS is not a generic substitute for infection for the pharmacokinetic evaluation of drugs.

The impact of Actinobacillus pleuropneumoniae (APP) infection in swine on the pharmacokinetic parameters of enrofloxacin were determined. Twenty-four animals were used in a 2 ϫ 2 factorial of treatment groups (six animals per group) to determine the impact of APP-induced inflammation and the antiinflammatory drug dexamethasone on enrofloxacin pharmacokinetic parameters. All animals received enrofloxacin as a single intravenous dose (5 mg/kg). Administration of dexamethasone was associated with an increase in clearance of enrofloxacin Clearance of enrofloxacin was not affected by APP. Volume of distribution at steady state was significantly increased in the dexamethasone-treated pigs. Volume of distribution at steady state was decreased by APP infection. Dexamethasone significantly increased the terminal elimination half-life of enrofloxacin. APP infection decreased the terminal elimination half-life of enrofloxacin in the infected pigs. Infection and dexamethasone significantly decreased the urine enrofloxacin/creatinine and ciprofloxacin/creatinine ratios. This study shows that APP infection does affect plasma pharmacokinetic parameters. Dexamethasone and APP infection may reduce renal clearance of enrofloxacin with a compensatory increase in intestinal clearance. Neither infection nor dexamethasone altered the metabolism of enrofloxacin to ciprofloxacin, the principal metabolite of enrofloxacin.

In this study, a polymerase chain reaction (PCR) primer set capable of amplifying a mitochondrial DNA segment of multiple species (cattle, sheep, goats, deer, and elk) whose rendered remains are prohibited from being fed to ruminants was characterized. However, the primer set also amplifies DNA derived from the rendered remains of pigs and horses, which are exempt from the feed ban. PCR amplicons derived from pig DNA have a restriction endonuclease site recognized by Hinf1, while the horse DNA-derived amplicon has a unique restriction endonuclease site recognized by HypCH4III. This "universal" PCR primer produced an amplicon with DNA extracted from dairy feed containing either bovine meat and bone meal or pig blood meal. Enzymatic digestion of the PCR amplicons from these feed samples with Hinf1 resulted in cleavage products only from samples containing pig blood meal. However, Hinf1 digestion of these amplicons was not complete. Further analysis of the pig blood meal with primers specific for bovine or porcine DNA demonstrated the presence of both bovine- and porcine-derived DNA. Enzymatic digestion confirmed these findings. Additional testing was conducted with dry dog food samples labeled as containing either lamb, chicken, turkey, or chicken and fish. The universal PCR primer produced an amplicon only for the dog food containing lamb meal. This paper is the first to describe a simplified approach for the detection of the prohibited species of concern in the feed ban.