Effects of endotoxin-induced mastitis on the pharmacokinetic properties of aditoprim in dairy cows.
Plasma disposition of aditoprim, a new dihydrofolate reductase inhibitor, was studied in healthy cows and cows with endotoxin-induced mastitis. A single dose of 5 mg of aditoprim/kg of body weight was administered IV to 5 healthy cows and to the same cows 3 weeks later at 2 hours after intramammary infusion of 0.1 mg of endotoxin into the rear quarters. Mastitis developed in all endotoxin-infused quarters and cows had systemic signs of disease (fever, tachycardia, depression) from 2 to 10 hours after infusion of endotoxin. Pharmacokinetic characteristics of aditoprim in healthy cows were a large volume of distribution (6.28 L/kg), a systemic clearance of 0.82 L/h/kg, and an elimination half-life of 7.26 hours. In cows with mastitis, plasma concentrations of aditoprim were lower between 5 and 26 hours after injection. The systemic clearance (1.00 L/h/kg) and the volume of distribution (12.25 L/kg) were significantly higher in cows with mastitis, but elimination half-life was not significantly different. The lower plasma concentrations of aditoprim between 5 and 26 hours after injection in cows with mastitis are explained by fluid compartment shifts and/or blood flow changes induced by mastitis, although increased elimination of aditoprim in cows with mastitis cannot completely be ruled out. The antibacterial activity of aditoprim is nearly the same as that of trimethoprim. The longer elimination half-life time of aditoprim, however, indicates that it may have a practical pharmacotherapeutic advantage over trimethoprim.
Lohuis
J A
JA
Department of Herd Health and Reproduction, College of Veterinary Medicine, State University of Utrecht, Yalelaan, The Netherlands.
Sutter
H M
HM
Graser
T
T
Ludwig
B
B
van Miert
A S
AS
Rehm
W F
WF
Rohde
E
E
Schneider
B
B
Wanner
M
M
van Werven
T
T
D000818:Animals; D002417:Cattle; D004731:Endotoxins; D005260:Female; D007501:Iron / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects / Q000662:veterinary; D008414:Mastitis, Bovine / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D014295:Trimethoprim / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D015032:Zinc / Q000097:blood
D004731:Endotoxins; C051398:aditoprim; D014295:Trimethoprim; D007501:Iron; D015032:Zinc