Comparison of two methods for determining the toxicokinetics of fluazifop-butyl after intravenous dosing in rats.
1. We have described and compared the use of two blood sampling techniques to measure the kinetics of fluazifop-butyl, a selective herbicide. Following intravenous administration of radiolabelled compound, blood samples were collected from female rats either by tail vein puncture or from chronically implanted catheters inserted in tethered rats. Urine samples were also collected from tethered animals. 2. Both techniques indicate that fluazifop-butyl is rapidly eliminated from blood into urine (t(1/2)3-4.5 h) and the overall blood concentration profiles were comparable between the two methods. However, by using cannulated rats, kinetic data were obtained from individual animals, providing evidence of inter-animal variation and allowing compartmental and statistical analysis. 3. The tethered rat technique is relatively simple and reliable. Compared to tail vein bleeding, results obtained from cannulated animals are more informative, providing comprehensive data from a small number of rats. It is therefore the preferred method for our kinetic based research studies using compounds known to exhibit multicompartmental elimination kinetics.
Rawlings
J M
JM
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Provan
W M
WM
Wilks
M F
MF
Batten
P L
PL
D000818:Animals; D001800:Blood Specimen Collection; D005260:Female; D006540:Herbicides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D006868:Hydrolysis; D007275:Injections, Intravenous; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D012044:Regression Analysis
D006540:Herbicides; D011725:Pyridines; C050585:fluazifop-butyl