Influence of porcine Actinobacillus pleuropneumoniae infection and dexamethasone on the pharmacokinetic parameters of enrofloxacin.
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 x 2 factorial of treatment groups (six animals per group) to determine the impact of APP-induced inflammation and the anti-inflammatory 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.
Post
Lynn O
LO
Division of Surveillance, Office of Surveillance and Compliance, Food and Drug Administration, Rockville, Maryland, USA.
Cope
Carol V
CV
Farrell
Dorothy E
DE
Baker
John D
JD
Myers
Michael J
MJ
D000189:Actinobacillus Infections / Q000378:metabolism* / Q000382:microbiology; D016977:Actinobacillus pleuropneumoniae; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D000077422:Enrofloxacin; D024841:Fluoroquinolones; D008297:Male; D015363:Quinolones / Q000493:pharmacokinetics*; D013552:Swine; D013553:Swine Diseases / Q000378:metabolism* / Q000382:microbiology
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D024841:Fluoroquinolones; D015363:Quinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin; D003907:Dexamethasone; D003404:Creatinine