Asunto(s)
Dibenzotiepinas/metabolismo , Animales , Biotransformación , Encéfalo/metabolismo , Dióxido de Carbono/biosíntesis , Isótopos de Carbono , Fenómenos Químicos , Química , Dibenzotiepinas/administración & dosificación , Dibenzotiepinas/análisis , Dibenzotiepinas/sangre , Dibenzotiepinas/orina , Sistema Digestivo/análisis , Heces/análisis , Mucosa Gástrica/metabolismo , Inyecciones Intravenosas , Intestino Grueso/metabolismo , Intestino Delgado/metabolismo , Intubación Gastrointestinal , Riñón/metabolismo , Cinética , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Músculos/metabolismo , Miocardio/metabolismo , Piperazinas/administración & dosificación , Piperazinas/análisis , Piperazinas/sangre , Piperazinas/metabolismo , Piperazinas/orina , Ratas , Piel/metabolismo , Especificidad de la Especie , Sulfatos/biosíntesis , Sulfóxidos/biosíntesis , Isótopos de Azufre , Ácidos Sulfúricos/biosíntesisRESUMEN
[14C]Tiopinac disposition was evaluated in man, monkey, rabbit, mouse, minipig, and rat. The absorption of tiopinac was rapid and essentially complete in these species. Peak plasma levels occurred in less than 1 hr to 2 hr in all species. Following iv and po doses, tiopinac was recovered predominantly in the urine. In man, 93.2 and 2.6% of the administered radioactivity was recovered in the urine and feces, respectively. In the rat, 61.3% of the radioactivity was accounted for in urine and 32.7% in feces. In the mouse, radioactivity was concentrated in the kidney and liver, with tissue/plasma ratios ranging from 1.3 to 7.0 for kidney and 0.5 to 1.7 for liver. Radioactivity in all other tissues was generally lower than in plasma. Tiopinac was shown to be the major circulating entity in plasma, accounting for 90% of total radioactivity levels in the mouse and 61% in the rat. The half-life of tiopinac was 2.3 +/- 0.3 hr in man, 0.8 hr in the minipig, and 2.6 hr in the rabbit. The volume of distribution was 0.29 +/- 0.05 liter/kg in man, 0.16 liter/kg in the rabbit and minipig, and 0.42 liter/g in the mouse. Tiopinac was highly bound (99.5%) in human serum.
Asunto(s)
Dibenzotiepinas/metabolismo , Absorción , Adulto , Animales , Antiinflamatorios , Dibenzotiepinas/sangre , Dibenzotiepinas/orina , Heces/análisis , Femenino , Semivida , Humanos , Cinética , Macaca fascicularis , Masculino , Ratones , Unión Proteica , Conejos , Ratas , Especificidad de la Especie , Porcinos , Distribución TisularRESUMEN
A method for the determination of isofloxythepin in biological fluids by gas chromatography-mass spectrometry is described. Isofloxythepin was readily converted into the trimethylsilyl ether by treatment with N,O-bis(trimethylsilyl)trifluoroacetamide. This derivative was separated on a 5% OV-101 column and determined, employing newly prepared isofloxythepin-d7 as an internal standard. Clean-up of isofloxythepin in blood and urine was efficiently achieved by back-extraction with hexane or hexane-toluene (9:1) under acidic and basic conditions, while isofloxythepin glucuronide in biological fluids was isolated by ion-exchange chromatography on Dowex 50W-X4 resin. The detection limit of isofloxythepin by this method was 50 pg. The blood and urine levels of isofloxythepin after oral administration of the drug to dogs were monitored by the proposed method.