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Measurement and pharmacokinetic study of unbound tropisetron in rat blood by microdialysis with high-performance liquid chromatography

1999; Elsevier BV; Volume: 182; Issue: 2 Linguagem: Inglês

10.1016/s0378-5173(99)00079-4

1873-3476

Chien-Tsai Huang, Chieh-Fu Chen, Tung-Hu Tsai,

Cancer therapeutics and mechanisms

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 μg/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 μg/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.