Stability and pharmacokinetics of flumazenil in the rat.
作者： Jaap W. Mandema , Josy M. Gubbens-Stibbe , Meindert Danhof
DOI: 10.1007/BF02244294
关键词: Antagonist 、 Bioavailability 、 Oral administration 、 Flumazenil 、 Half-life 、 Pharmacology 、 Chemistry 、 Sodium fluoride 、 Distribution (pharmacology) 、 Pharmacokinetics
摘要: The pharmacokinetics of flumazenil in the rat were determined after 2.5 mg/kg intravenous and 25 oral administration. Following administration was rapidly eliminated with an extremely short terminal half-life (mean±SE,n=8) 8.3±0.3 min due to a large total blood clearance 147±7 ml/kg/min combined relatively small volume distribution at steady-state 1.33±0.07 l/kg. After absorbed; however, bioavailability low (28±4%) variable. Flumazenil found be unstable vitro disappeared (mean±SE,n=5) 8.3±1 31±4 body room temperature, respectively. samples stabilized by addition sodium fluoride (NaF) cooling 0°C. had stored −35°C when analyzed later times. Presumably esterases are responsible for observed instability. A sensitive HPLC assay measure concentrations is also described.
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