Roncari G, Ziegler W H, Guentert T W
Br J Clin Pharmacol. 1986 Oct;22(4):421-8. doi: 10.1111/j.1365-2125.1986.tb02912.x.
During clinical pharmacology studies with the benzodiazepine antagonist Ro 15-1788 the pharmacokinetic characteristics of high intravenous doses (20 and 40 mg) and of an oral dose (200 mg) were examined in six healthy male volunteers. Ro 15-1788 was rapidly and extensively distributed in the body with an apparent volume of distribution Vss of 1.06 l kg-1. Elimination occurred rapidly by hepatic metabolism and the high plasma clearance of 1.14 l min-1 resulted in a short elimination half-life of less than 1 h. No difference in the disposition parameters calculated from the data after the 20 and 40 mg doses was observed reflecting a dose-proportionality in the areas under plasma concentration-time curves and unchanged distribution characteristics. Because the blood/plasma distribution coefficient is close to unity the disposition parameters obtained from plasma concentrations are similar to the corresponding parameters with reference to blood. Following oral administration of 200 mg the drug is rapidly absorbed. Peak levels were reached after 20-90 min and were close to or even higher than the values after the 40 mg intravenous dose at the same time point. Due to the high hepatic extraction ratio the fraction reaching the systemic circulation unchanged was reduced to approximately 16% during the absorption step.
在使用苯二氮䓬拮抗剂Ro 15 - 1788进行临床药理学研究时，对6名健康男性志愿者检测了高静脉剂量（20毫克和40毫克）及口服剂量（200毫克）的药代动力学特征。Ro 15 - 1788在体内迅速且广泛分布，其稳态分布容积Vss为1.06升/千克。通过肝脏代谢迅速消除，血浆清除率高，为1.14升/分钟，导致消除半衰期短于1小时。20毫克和40毫克剂量后数据计算得出的处置参数未观察到差异，反映出血浆浓度 - 时间曲线下面积的剂量比例关系以及分布特征未改变。由于血/血浆分布系数接近1，从血浆浓度获得的处置参数与参照血液的相应参数相似。口服200毫克后药物迅速吸收。20 - 90分钟后达到峰值水平，且在同一时间点接近甚至高于40毫克静脉注射剂量的值。由于肝脏提取率高，吸收过程中未改变进入体循环的部分降至约16%。
