Measurement and pharmacokinetic study of unbound tropisetron in rat blood by microdialysis with high-performance liquid chromatography.
A microdialysis system coupled with liquid chromatography was applied for the measurement of unbound tropisetron in rat blood. The microdialysis probe was inserted into a jugular vein/right atrium of male Sprague-Dawley rats. Tropisetron (5 or 10 mg/kg, i.v.) was then administered via a femoral vein of rat. Samples were eluted with a mobile phase containing acetonitrile-100 mM monosodium phosphate (pH 5.0, 26:74, v/v). The UV detector wavelength was set at 284 nm. The detection limit of tropisetron was 20 ng/ml. The in vivo recovery of microdialysis probe in rat jugular vein/atrium for tropisetron at 1, 2, and 5 microg/ml were between 49 and 53% (n=5). Intra- and inter-assay accuracy and precision of the analyses were <10% in the range of 0.1-1 microg/ml. The method has been applied to pharmacokinetic analysis of unbound tropisetron in rat intravenous administration. Rapid distribution followed by a slower elimination phase was observed from the blood concentration-time curve. The disposition of tropisetron at each dose fitted well to a two-compartment model.
Huang
C T
CT
Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan, ROC.
Chen
C F
CF
Tsai
T H
TH
D000818:Animals; D000932:Antiemetics / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077526:Tropisetron
D000932:Antiemetics; D007211:Indoles; D000077526:Tropisetron