Pharmacokinetics of Octreotide in PatientsWith Cirrhosis and Portal Hypertension;Relationship Between the Plasma Levelsof the Analogue and the Magnitudeand Duration of the Reduction in CorrectedWedged Hepatic Venous Pressure

摘要

In healthy subjects octreotide is largely metabolisedby the liver suggesting that the plasma half-life of thesomatostatin analogue may be prolonged in patientswith hepatic dysfunction. The aim of this study wastherefore (a) to determine the pharmacokinetics ofoctreotide following its subcutaneous injection in 6patients with cirrhosis and portal hypertension and(b) compare the magnitude and duration of the effectsof intravenous administration of 250 μg somatostatinand 50 μg octreotide on corrected wedged hepaticvenous pressure (WHVP) and to relate the findings tothe plasma levels of the analogue 1h after administrationin 13 patients with cirrhosis and portalhypertension. Following subcutaneous administrationof 50 μg octreotide the circulating half life (range2.4 to 4.79 h) was prolonged whereas the clearance(range 2.101 to 4.775 L/h) was decreased compared tohealthy controls. Intravenous bolus administration of25 μg somatostatin or 50 μg octreotide resulted in areduction in WHVP of approximately the samemagnitude and duration despite appreciable quantitiesof the analogue in the blood lh after administration(1944 ± 226 pg/ml). These results indicatethat the circulating half-life of octreotide is prolongedin cirrhotics suggesting that the dosageregimens should be modified in such patients toavoid accumulation of the analogue in the bloodwhich may result in undesirable side-effects ortoxicity. Furthermore, since the magnitude andduration of the reduction in WHVP elicited by IVoctreotide is similar to that obseved with somatostatin,the analogue, like the native hormone, must beadministered by continuous IV infusion to produce asustained response and hence a therapeutic effect inthe management of acute variceal bleeding.