Weeke J, Christensen S E, Orskov H, Kaal A, Pedersen M M, Illum P, Harris A G
Medical Department M (Endocrinology and Diabetes), University of Aarhus, Kommunehospital, Denmark.
J Clin Endocrinol Metab. 1992 Jul;75(1):163-9. doi: 10.1210/jcem.75.1.1619006.
Fifteen acromegalic patients received four single doses of octreotide in random order (500 micrograms, 1000 micrograms, and 2000 micrograms applied intranasally and 100 micrograms given sc). Serum octreotide and GH data were subjected to pharmacokinetic analyses, and local nasal effects were evaluated by acoustic rhinometry. Average areas (+/- SEM) under the serum octreotide curves were: 2000 micrograms: 4597 +/- 536; 1000 micrograms: 1923 +/- 439; 500 micrograms: 957 +/- 168; and 100 micrograms sc: 896 +/- 81 micrograms.L-1.min (n = 13). The calculated relative availability was 27% +/- 0.03; 22% +/- 0.05; 22% +/- 0.03, respectively, for the three nasal doses. The rate of absorption after intranasally administered octreotide was greater than after sc application: t1/2 ka: 7.1 +/- 1.6; 7.9 +/- 1.6; 11.3 +/- 1.9, respectively, vs. 24.1 +/- 2.5 min, whereas the rates of disappearance were similar. GH suppression started immediately after application and reached minimum levels 1-2 h later. The average intervals during which serum GH was below 50% of preadministration values were: 2000 micrograms: 544 +/- 47; 1000 micrograms: 423 +/- 56; 500 micrograms: 289 +/- 52 vs. 351 +/- 34 min after sc injection of 100 micrograms. With 2000 micrograms intranasally all but one of the 15 patients attained constant suppression of serum GH below 5 micrograms/L for 273 to 680 min. Pharmacokinetic analysis demonstrated that 100 micrograms sc and 1000 micrograms intranasally induced the same GH suppressive effect and that 2000 micrograms intranasally approximately doubled the duration of action. Acoustic rhinometry was performed after nasal application of the largest dose of 2000 micrograms and after carrier (n = 9). A highly significant tumescence of the nasal mucosa was maximal after 10 min and gradually receded over the next 2 h. However, this was felt by the patients to be acceptable. The effect was caused by octreotide per se and was probably due to vasodilation.
15例肢端肥大症患者随机接受4次单剂量的奥曲肽（分别经鼻给予500微克、1000微克和2000微克，皮下注射100微克）。对血清奥曲肽和生长激素（GH）数据进行药代动力学分析，通过鼻声反射测量法评估局部鼻腔效应。血清奥曲肽曲线下的平均面积（±标准误）分别为：2000微克组：4597±536；1000微克组：1923±439；500微克组：957±168；皮下注射100微克组：896±81微克·升⁻¹·分钟（n = 13）。计算得出三种经鼻剂量的相对生物利用度分别为27%±0.03；22%±0.05；22%±0.03。经鼻给予奥曲肽后的吸收速率大于皮下给药：达峰时间（t1/2 ka）分别为7.1±1.6；7.9±1.6；11.3±1.9分钟，而皮下注射为24.1±2.5分钟，不过消除速率相似。应用奥曲肽后GH抑制立即开始，1 - 2小时后达到最低水平。血清GH低于给药前值50%的平均持续时间分别为：2000微克组：为544±47分钟；1000微克组：423±56分钟；500微克组：289±52分钟，而皮下注射100微克后为351±34分钟。经鼻给予2000微克时，15例患者中除1例之外，其余患者血清GH均持续抑制至5微克/升以下，持续273至680分钟。药代动力学分析表明，皮下注射100微克和经鼻给予1000微克诱导相同的GH抑制效果，经鼻给予2000微克使作用持续时间约增加一倍。在鼻内给予最大剂量2000微克奥曲肽后以及给予载体后（n = 9）进行鼻声反射测量法检查。鼻黏膜出现高度显著的肿胀，在10分钟时达到最大程度，随后在接下来的2小时内逐渐消退。不过，患者认为这种情况可以接受。这种效应是由奥曲肽本身引起的，可能是由于血管舒张所致。
