Effects of experimentally induced Pasteurella haemolytica infection in dairy calves on the pharmacokinetics of flumequine.
The effect of experimental Pasteurella haemolytica infection on the intravenous and intramuscular pharmacokinetics of flumequine was studied in dairy calves. The plasma concentration-time curve of flumequine after intravenous injection of 5 mg/kg bodyweight flumequine of a 10% solution before and after experimental infection, was best described by a three-compartment open model. After intramuscular injection of the same dosage rate of a 3% flumequine suspension is was best described by the one-compartment open model with first-order absorption. The experimental infection by intratracheal administration of infectious bovine rhinotracheitis (IBR)-virus and 5 days later intrapulmonary administration of Pasteurella haemolytica produced a clear temperature rise and signs of disease expressed as Average Health Status. Subsequently, plasma Fe and Zn concentration decreased after infection. The distribution volumes Vc, Vd(area) and Vd(ss) after infection (0.07 +/- 0.04, 1.38 +/- 0.36 and 0.50 +/- 0.11 l/kg, respectively) were smaller than those before infection, but the differences were not significant (P less than or equal to 0.1). The intravenous AUC infinity was significantly increased (21.86 +/- 3.51 to 33.85 +/- 2.97 mg.h/l, P less than or equal to 0.01) and the total body clearance (ClB) significantly decreased (0.24 +/- 0.02 to 0.15 +/- 0.01, P less than or equal to 0.01) after infection. After intramuscular injection of flumequine at 5 mg/kg as a 3% suspension, only the bioavailability, F, was significantly decreased after infection (78.5 +/- 14.3 to 59.7 +/- 21.2%, P less than or equal to 0.02). However, this had no consequences for the dosage regimen used. The urine concentration ratio flumequine:7-hydroxy-flumequine:conjugated flumequine changed from 2:1:10 before infection to 6:1:15 after infection, which indicates that hydroxylation and glucuronidation as metabolic pathways for flumequine were decreased after Pasteurella sp. infection.
Department of Large Animal Medicine and Nutrition, Veterinary Faculty, University of Utrecht, The Netherlands.
D J
DJ
Mevius
H J
HJ
Breukink
A S
AS
van Miert
B G
BG
Kessels
A S
AS
Jobse
J A
JA
Smit
D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D001831:Body Temperature; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism*; D024841:Fluoroquinolones; D006207:Half-Life; D006304:Health Status; D006863:Hydrogen-Ion Concentration; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007501:Iron / Q000097:blood; D007958:Leukocyte Count / Q000662:veterinary; D008297:Male; D016978:Mannheimia haemolytica; D010326:Pasteurella Infections / Q000378:metabolism / Q000662:veterinary*; D011807:Quinolizines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D013046:Specific Gravity; D014018:Tissue Distribution; D015032:Zinc / Q000097:blood
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011807:Quinolizines; D007501:Iron; D015032:Zinc; C012976:flumequine