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

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

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^(14)C标记CT-707,单次给予6名健康男性受试者300 mg(120μci)[^(14)C]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[^(14)C]CT-707552 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:AUC_(0-t)为(1049.15±589.38)ng·Equ.g^(-1)·h,AUC_(0-∞)为(2288.64±511.05)ng·Equ.g^(-1)·h,C_(max)为(229.00±63.66)ng/Equ.g,T_(max)和t_(1/2)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。

AIM:To study the absorption and excretion of CT-707 in healthy male subjects.METHODS:Six healthy male subjects received a single 300 mg(120μCi)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-707552 h(23 d)as a suspension in a fasted state,the mean AUC_(0-t),AUC_(0-∞),C_(max),T_(max) and t_(1/2) values for CT-707 in plasma were(1049.15±589.38)ng·Equ.g^(-1)·h,(2288.64±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.