论文部分内容阅读
目的用放射性核素示踪技术研究TRAIL在大鼠体内的药动学特性。方法大鼠15只,随机分成3组,分别给予以Iodogen法制备的125ITRAIL1.5、5及15mg·kg-1,iv,于不同时相取血测放射性计数,计算相应的血药浓度并以3P87软件处理计算主要的药动学参数。结果制备了符合药动学研究要求的125ITRAIL,其放化纯度>98%。在大鼠体内均可以二室模型拟合血药浓度的动态变化。低、中、高3个剂量的T1/2(α)分别为(5.69±1.39)、(5.84±1.20)、(6.34±0.74)min;T1/2(β)分别为(46.25±11.96)、(47.61±15.07)、(64.64±8.94)min;AUC0→t分别为(120.80±22.42)、(915.70±409.10)、(3991.00±2193.00)mg·min·L-1。经统计分析,T1/2(β)、MRT、CL(s)在3个剂量组间差异无统计学意义(P>0.05),T1/2(β)在高剂量时明显延长;AUC0→t随着剂量增加而显著增加(P<0.05),但是AUC0→t与剂量的比值在低、中剂量、中剂量和高剂量间差异无统计学意义(P>0.05),而低剂量和高剂量间差异有统计学意义(P<0.05)。125ITRAIL1.5mg·kg-1,iv,在大鼠体内分布广泛。排泄试验显示120h后经尿和粪排泄的放射活性及甲状腺组织富集的碘近82%。结论125ITRAIL在低剂量和中剂量时符合线性动力学特征,到高剂量时逐步向非线性动力学过渡;1.5mg·kg-1,iv,肾脏中放射活?
Objective To study the pharmacokinetics of TRAIL in rats by radionuclide tracer technique. Methods Fifteen rats were randomly divided into three groups. The rats were given 125ITRAIL 1.5, 5 and 15 mg · kg-1, iv respectively by Iodogen method. The radioactivity was measured at different time points and the corresponding plasma concentration was calculated The 3P87 software handles the calculation of the main pharmacokinetic parameters. Results 125ITRAIL was prepared according to the requirements of pharmacokinetics. Its radiochemical purity was> 98%. In rats, two-compartment model can be used to fit the dynamic changes of plasma concentration. T1 / 2 (α) in low, medium and high doses were (5.69 ± 1.39), (5.84 ± 1.20) and (6.34 ± 0.74) min, respectively; (47.61 ± 15.07) and (64.64 ± 8.94) min, respectively; AUC0 → t were (120.80 ± 22.42), (915.70 ± 409.10) and (3991.00 ± 2193.00) mg · min · L-1, respectively. The statistical analysis showed that T1 / 2 (β), MRT and CL (s) had no significant difference among the three dose groups (P> 0.05). T1 / 2 (P <0.05), but there was no significant difference between AUC0 → t and dose (P> 0.05), but there was no significant difference between middle dose, middle dose and high dose (P> 0.05) The difference was statistically significant (P <0.05). 125ITRAIL1.5mg · kg-1, iv, widely distributed in rats. Excretion tests showed radioactive excretion of excreted urine and excreted radioactivity by 120% and iodine-enriched iodine in the thyroid tissue nearly 82%. Conclusion 125ITRAIL at low and medium doses in line with the linear kinetic characteristics, to a high dose gradually transition to nonlinear dynamics; 1.5mg · kg-1, iv, renal radioactivity?