Gingell R, Beatty P W, Mitschke H R, Page A C, Sawin V L, Putcha L, Kramer W G
Toxicology Department, Shell Oil Company, Houston, Texas 77210.
Toxicol Appl Pharmacol. 1987 Dec;91(3):386-94. doi: 10.1016/0041-008x(87)90060-3.
The objective of this study was to determine the kinetics of absorption, distribution, and elimination of DBCP after intravenous (iv) administration in plasma, and after oral administration in water or corn oil, to conscious, fed, male Fischer 344 rats. Rats were prepared with an external jugular vein cannula and were dosed with 0.1, 1, or 10 mg/kg DBCP into the penile sinus or orally as a solution in water or in corn oil (1 mg/kg only). Blood was sampled at various times up to 12 hr, concentrations of DBCP were determined by gas chromatography, and data were evaluated by classical pharmacokinetic techniques. After oral administration in water, absorption of DBCP was rapid, and the distribution and elimination phase was biexponential. There did not appear to be any saturation of DBCP absorption, distribution, or elimination at the high oral or iv dose. After oral administration of DBCP in a corn oil vehicle, absorption was prolonged, suggesting retention of DBCP in the stomach; this could contribute to the toxic effects of DBCP on the forestomach when chronically administered in corn oil. The areas under the blood concentration/time curve were similar regardless of vehicle, suggesting that systemic toxicity might be independent of the vehicle.
本研究的目的是测定在清醒、进食的雄性Fischer 344大鼠中,静脉注射(iv)后DBCP在血浆中的吸收、分布和消除动力学,以及口服水或玉米油后DBCP的吸收、分布和消除动力学。给大鼠制备颈外静脉插管,分别以0.1、1或10 mg/kg的DBCP剂量注入阴茎窦,或以水或玉米油溶液(仅1 mg/kg)口服给药。在长达12小时的不同时间采集血液样本,通过气相色谱法测定DBCP浓度,并采用经典药代动力学技术对数据进行评估。口服水后,DBCP吸收迅速,分布和消除阶段呈双指数。在高口服或静脉注射剂量下,DBCP的吸收、分布或消除似乎没有出现任何饱和现象。以玉米油为载体口服DBCP后,吸收延长,提示DBCP在胃中潴留;长期以玉米油给药时,这可能导致DBCP对前胃的毒性作用。无论载体如何,血药浓度/时间曲线下面积相似,提示全身毒性可能与载体无关。