Pharmacokinetics of Octreotide in Patients With Cirrhosis and Portal Hypertension; Relationship Between the Plasma Levels of the Analogue and the Magnitude and Duration of the Reduction in Corrected Wedged Hepatic Venous Pressure
S. A. Jenkins, D. M. Nott, J. N. Baxter
1998 Volume 11, p13-21
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 μg somatostatin and 50 μg octreotide on corrected wedged hepatic venous pressure (WHVP) and to relate the findings to the plasma levels of the analogue 1h after administration in 13 patients with cirrhosis and portal hypertension. Following subcutaneous administration of 50 μg 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 25 μg somatostatin or 50 μg octreotide resulted in a reduction in WHVP of approximately the same magnitude and duration despite appreciable quantities of the analogue in the blood lh 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 obseved 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.
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