放射性同位素示踪法研究CT-707在健康男性受试者体内的吸收和排泄

目的：研究CT-707在健康男性受试者体内的吸收和排泄。方法：采用放射性同位素14C标记CT-707，单次给予6名健康男性受试者300 mg（120 μci）［14C］CT-707混悬制剂空腹口服，使用液体闪烁计数仪（LSC）测定血浆、粪便和尿液的总放射性，用WinNonlin（8.1版Pharsight）软件按非房室模型计算血浆中总放射性的药代动力学参数，根据各时间间隔收集尿液和粪便的重量及放射性物质浓度，计算尿液和粪便中总放射性的回收率。结果：6名健康男性受试者单次空腹口服300 mg ［14C］CT-707 552 h（23 d）后，血浆中总放射性的平均主要药代动力学参数如下：AUC0-t为（1 049.15±589.38） ng·Equ.g-1·h，AUC0-∞为（2 288.64±511.05） ng·Equ.g-1·h，Cmax为（229.00±63.66）ng/Equ.g，Tmax和t1/2分别为（2.83±1.47）h和（6.17±2.43）h。排泄试验结果显示：CT-707主要从粪便中排泄，粪便平均累计回收率约为（76.24±3.43）%，部分从尿液中排泄，平均累计回收率约为（3.41±1.00）%，总的平均累计回收率约为（79.65±3.26）%。CT-707耐受性良好，未报告严重的不良事件。结论：健康男性受试者单次空腹口服CT-707混悬制剂后，吸收迅速，消除较快，大部分通过粪便回收，安全性及耐受性好。

Absorption and excretion of CT-707 in healthy male subjects studied by radioisotope tracer method

AIM: To study the absorption and excretion of CT-707 in healthy male subjects. METHODS: Six healthy male subjects received a single 300 mg (120 μCi) oral dose of radio-labeled CT-707 as a suspension in a fasted state. Blood, urine and feces were collected. Radioactivity concentrations were measured by liquid scintillation counting (LSC). The pharmacokinetic parameters of total radioactivity in plasma were calculated by WinNonlin (Pharsight version 8.1) software according to the non-compartment model. The recovery rate of total radioactivity in urine and feces was calculated according to the weight and radioactivity concentration of urine and feces collected at each time interval. RESULTS: After a single 300 mg oral of radio-labeled CT-707 552 h (23 d) as a suspension in a fasted state, the mean AUC0-t, AUC0-∞, Cmax, Tmax and t1/2 values for CT-707 in plasma were (1 049.15±589.38) ng·Equ.g-1·h, (2 288.64±511.05) ng·Equ.g-1·h, (229.00±63.66) ng/Equ.g, (2.83±1.47) h and (6.17±2.43) h, respectively. Excretion test results showed that CT-707 was mainly excreted from feces with a mean cumulative recovery of about (76.24±3.43)%, and partial excreed from urine with a mean cumulative recovery of about (3.41±1.00)%, and a total mean cumulative recovery of about (79.65±3.26)%. CT-707 was well tolerated and no serious adverse events were reported. CONCLUSION: In healthy male subjects, CT-707 suspension preparation can be absorbed quickly and eliminated quickly after a single oral in a fasted state. Most of the suspension preparation can be recovered through feces, showing good safety and tolerated.