DeBold C R, Sheldon W R, DeCherney G S, Jackson R V, Nicholson W E, Island D P, Orth D N
J Clin Endocrinol Metab. 1985 May;60(5):836-40. doi: 10.1210/jcem-60-5-836.
Long term use of ovine corticotropin-releasing hormone (oCRH) requires a convenient route of administration. The effects of 0.3, 3, and 30 micrograms/kg BW synthetic oCRH given as a sc injection and of 10 and 30 micrograms/kg given as an intranasal spray were studied in 10 normal men in the late afternoon. Basal plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol levels were 14 +/- 1.9 pg/ml and 4.3 +/- 0.4 microgram/dl (mean +/- SEM). Peak IR-ACTH levels (mean +/- SEM) were 43 +/- 5.5, 53 +/- 8.1, and 64 +/- 8.9 pg/ml after the 0.3, 3, and 30 micrograms/kg doses of oCRH given sc, respectively, and 23 +/- 4.3 and 36 +/- 4.8 pg/ml after the 10 and 30 micrograms/kg doses of oCRH given intranasally, respectively. The lowest sc dose and both intranasal doses caused only single IR-ACTH peaks. After 3 and 30 micrograms/kg sc oCRH, IR-ACTH rose by 15 min, reached an initial peak at 45-60 min, fell rapidly until 90-120 min, and rose to a second peak at 3-5 h. This biphasic response is similar to that previously found after iv administration. IR-ACTH levels remained elevated for 4, 10, and at least 16 h after 0.3, 3, and 30 micrograms/kg sc oCRH, respectively, and for 1.5 and 3 h after 10 and 30 micrograms/kg intranasal oCRH respectively. The effect on IR-cortisol was similar, but more prolonged. Compared to the iv route, sc oCRH produced similar mean peak IR-ACTH and IR-cortisol levels and had a slightly longer duration of action. Intranasal oCRH was only about 1% as effective. Peak plasma IR-oCRH levels in 2 subjects receiving 3 micrograms/kg sc oCRH were 13 and 17 ng/ml at 90 min. These peaks were lower than those after iv administration of the same dose, but the levels remained elevated longer, probably accounting for the longer duration of action of sc oCRH. Peak plasma IR-oCRH levels in 4 subjects given 10 microgram/kg intranasal oCRH were only 64-122 pg/ml, presumably reflecting poor absorption through the nasal mucosa. These results demonstrate that sc injection of oCRH is at least as effective as the iv route with respect to plasma IR-ACTH and IR-cortisol responses. The convenience of this route of administration and the prolonged duration of action of oCRH suggest the feasibility of long term oCRH use.
长期使用绵羊促肾上腺皮质激素释放激素（oCRH）需要一种便捷的给药途径。在傍晚时分，对10名正常男性研究了皮下注射给予0.3、3和30微克/千克体重的合成oCRH以及鼻内喷雾给予10和30微克/千克的效果。基础血浆免疫反应性促肾上腺皮质激素（IR-ACTH）和IR-皮质醇水平分别为14±1.9皮克/毫升和4.3±0.4微克/分升（均值±标准误）。皮下给予0.3、3和30微克/千克剂量的oCRH后，IR-ACTH峰值水平（均值±标准误）分别为43±5.5、53±8.1和64±8.9皮克/毫升，鼻内给予10和30微克/千克剂量的oCRH后，分别为23±4.3和36±4.8皮克/毫升。最低的皮下剂量和两种鼻内剂量仅引起单个IR-ACTH峰值。皮下给予3和30微克/千克oCRH后，IR-ACTH在15分钟时升高，在45 - 60分钟时达到初始峰值，迅速下降直至90 - 120分钟，并在3 - 5小时时升至第二个峰值。这种双相反应与之前静脉注射后发现的反应相似。皮下给予0.3、3和30微克/千克oCRH后，IR-ACTH水平分别在4、10和至少16小时内保持升高，鼻内给予10和30微克/千克oCRH后，分别在1.5和3小时内保持升高。对IR-皮质醇的影响相似，但持续时间更长。与静脉途径相比，皮下给予oCRH产生的平均峰值IR-ACTH和IR-皮质醇水平相似，且作用持续时间稍长。鼻内给予oCRH的效果仅约为静脉途径的1%。2名接受3微克/千克皮下oCRH的受试者在90分钟时的血浆IR-oCRH峰值水平分别为13和17纳克/毫升。这些峰值低于相同剂量静脉注射后的峰值，但水平保持升高的时间更长，这可能解释了皮下给予oCRH作用持续时间更长的原因。4名给予10微克/千克鼻内oCRH的受试者的血浆IR-oCRH峰值水平仅为64 - 122皮克/毫升，这可能反映了通过鼻黏膜的吸收较差。这些结果表明，就血浆IR-ACTH和IR-皮质醇反应而言，皮下注射oCRH至少与静脉途径一样有效。这种给药途径的便利性以及oCRH作用持续时间的延长表明长期使用oCRH是可行 的。
