Rafferty B, Poole S, Clarke R, Schulster D
J Endocrinol. 1985 Dec;107(3):R5-8. doi: 10.1677/joe.0.107r005.
A homologous radioimmunoassay (RIA) system for human growth hormone-releasing factor 1-29NH2 (hGRF 1-29-NH2) was developed and applied to the measurement of immunoreactive (IR) concentrations of the peptide in anaesthetized rats to determine some of its pharmaco-kinetics after i.v. and s.c. administration. Analysis of the biphasic disappearance curve of IR-hGRF-1-29NH2 from plasma after i.v. injection (10 micrograms) gave values for the half-lives of the initial distribution phase (alpha) and for the elimination phase (beta) of 1.9 +/- 0.2 min and 10.4 +/- 0.2 min respectively. There was rapid uptake of the peptide from the site of s.c. injection but comparison of areas under the plasma IR-hGRF1-29NH2/time curves showed that the estimated total amount in the circulation after s.c. injection was only 4% of that obtained after i.v. administration. A large degree of degradation of the peptide is indicated either at the site of injection or during transfer to plasma; this susceptibility to rapid breakdown is reflected in the short half-life of the peptide in the circulation. Therefore the measurement of the above parameters is a prerequisite when assessing potency of GRF analogues in-vivo and when implementing suitable dosage regimens for clinical purposes.
开发了一种用于人生长激素释放因子1 - 29NH2(hGRF 1 - 29 - NH2)的同源放射免疫分析(RIA)系统,并将其应用于测定麻醉大鼠体内该肽的免疫反应性(IR)浓度,以确定静脉注射和皮下注射后其一些药代动力学参数。静脉注射(10微克)后,分析血浆中IR - hGRF - 1 - 29NH2的双相消失曲线,得出初始分布相(α)和消除相(β)的半衰期值分别为1.9±0.2分钟和10.4±0.2分钟。肽从皮下注射部位迅速吸收,但比较血浆IR - hGRF1 - 29NH2/时间曲线下的面积表明,皮下注射后循环中的估计总量仅为静脉注射后获得量的4%。这表明该肽在注射部位或转移到血浆过程中发生了大量降解;这种对快速分解的敏感性反映在该肽在循环中的半衰期较短。因此,在评估GRF类似物的体内效力以及为临床目的实施合适的给药方案时,测量上述参数是一个先决条件。