Jenkins S A, Nott D M, Baxter J N
University Department of Surgery, Royal Liverpool University Hospital.
HPB Surg. 1998;11(1):13-21. doi: 10.1155/1998/17436.
In healthy subjects octreotide is largely metabolised by the liver suggesting that the plasma half-life of the somatostatin analogue may be prolonged in patients with hepatic dysfunction. The aim of this study was therefore (a) to determine the pharmacokinetics of octreotide following its subcutaneous injection in 6 patients with cirrhosis and portal hypertension and (b) compare the magnitude and duration of the effects of intravenous administration of 250 micrograms somatostatin and 50 micrograms octreotide on corrected wedged hepatic venous pressure (WHVP) and to relate the findings to the plasma levels of the analogue 1 h after administration in 13 patients with cirrhosis and portal hypertension. Following subcutaneous administration of 50 micrograms octreotide the circulating half life (range 2.4 to 4.79 h) was prolonged whereas the clearance (range 2.101 to 4.775 L/h) was decreased compared to healthy controls. Intravenous bolus administration of 250 micrograms somatostatin or 50 micrograms octreotide resulted in a reduction in WHVP of approximately the same magnitude and duration despite appreciable quantities of the analogue in the blood 1 h after administration (1944 +/- 226 pg/ml). These results indicate that the circulating half-life of octreotide is prolonged in cirrhotics suggesting that the dosage regimens should be modified in such patients to avoid accumulation of the analogue in the blood which may result in undesirable side-effects or toxicity. Furthermore, since the magnitude and duration of the reduction in WHVP elicited by IV octreotide is similar to that observed with somatostatin, the analogue, like the native hormone, must be administered by continuous IV infusion to produce a sustained response and hence a therapeutic effect in the management of acute variceal bleeding.
在健康受试者中，奥曲肽主要由肝脏代谢，这表明在肝功能不全的患者中，生长抑素类似物的血浆半衰期可能会延长。因此，本研究的目的是：（a）确定6例肝硬化和门静脉高压患者皮下注射奥曲肽后的药代动力学；（b）比较静脉注射250微克生长抑素和50微克奥曲肽对校正肝静脉楔压（WHVP）的影响程度和持续时间，并将结果与13例肝硬化和门静脉高压患者给药后1小时类似物的血浆水平相关联。皮下注射50微克奥曲肽后，与健康对照相比，循环半衰期（范围为2.4至4.79小时）延长，而清除率（范围为2.101至4.775升/小时）降低。静脉推注250微克生长抑素或50微克奥曲肽导致WHVP降低的程度和持续时间大致相同，尽管给药后1小时血液中有相当数量的类似物（1944±226皮克/毫升）。这些结果表明，肝硬化患者中奥曲肽的循环半衰期延长，提示此类患者应调整给药方案，以避免类似物在血液中蓄积，这可能导致不良副作用或毒性。此外，由于静脉注射奥曲肽引起的WHVP降低的程度和持续时间与生长抑素相似，该类似物与天然激素一样，必须通过静脉持续输注给药，以产生持续反应，从而在急性静脉曲张出血的治疗中发挥治疗作用。
