Candas B, Lacoste D, Normand M, Labrie F
Department of Physiology, Faculty of Medicine, Laval University, Quebec, Canada.
J Clin Endocrinol Metab. 1990 Apr;70(4):1046-54. doi: 10.1210/jcem-70-4-1046.
The kinetics of plasma immunoreactive [D-Trp6,Des-Gly-NH2(10)]GnRH ethylamide, a potent GnRH agonist, was assessed in nine normal adult men over a period of 24 h after a rapid sc injection of 1 or 10 micrograms peptide/kg BW. The specific RIA of the GnRH agonist is characterized by a minimum detectable dose of 5.0 +/- 0.5 pg peptide, while the midrange effective dose is 73 +/- 8 pg. The within- and between-assay coefficients of variation range from 2-7% and from 10-15%, respectively. When the volume of the central compartment is set proportional to the logarithm of the plasma concentration of the GnRH agonist, the time courses of both doses are statistically well represented by a two-compartment model to which a source compartment is added to represent the sc route of administration. The sc diffusion to plasma is 5 times faster than any other fractional transport rate of the model (5%/min). Disposal occurs at a maximum rate of 0.55%/min from the central compartment, which includes plasma, and 0.25%/min from the peripheral compartment. As simulated with the model, 90% of the steady state is reached 13 h and 45 min after the onset of a sc continuous infusion. A molecule spends, on the average, from 6 h to 9 h and 45 min in the whole organism; 30-50% of this period is accounted for by residence in the central compartment. The volume of the central compartment reaches 208 mL/kg BW, and the MCR is estimated at 1.18 mL/min.kg BW for a steady state of 1 ng/mL plasma. The plasma dynamics of [D-Trp6,Des-Gly-NH2(10)]GnRH ethylamide in men are at least 10 times slower than those reported for the natural GnRH, thus indicating the relevance of its clinical use in suppressive therapy of LH secretion.
在9名正常成年男性中，快速皮下注射1或10微克肽/千克体重后24小时内，评估了一种强效促性腺激素释放激素（GnRH）激动剂——血浆免疫反应性[D-色氨酸6，去甘氨酸-NH2(10)]GnRH乙酰胺的动力学。GnRH激动剂的特异性放射免疫分析的特征在于最小可检测剂量为5.0±0.5皮克肽，而中等有效剂量为73±8皮克。批内和批间变异系数分别为2%-7%和10%-15%。当中央室的体积与GnRH激动剂血浆浓度的对数成比例设定时，两种剂量的时间进程在统计学上都能很好地用二室模型表示，并添加一个源室来代表皮下给药途径。皮下向血浆的扩散比模型的任何其他分数转运速率快5倍（5%/分钟）。清除发生的最大速率为中央室（包括血浆）的0.55%/分钟和外周室的0.25%/分钟。如模型模拟所示，皮下持续输注开始后13小时45分钟达到稳态的90%。一个分子在整个生物体中平均停留6小时至9小时45分钟；其中30%-50%的时间是在中央室停留。中央室的体积达到208毫升/千克体重，对于血浆稳态为1纳克/毫升，估计的平均驻留时间为1.18毫升/分钟·千克体重。男性中[D-色氨酸6，去甘氨酸-NH2(10)]GnRH乙酰胺的血浆动力学至少比天然GnRH报道的慢10倍，因此表明其在促黄体生成素分泌抑制治疗中的临床应用价值。
