Lanreotide effect on splanchnic blood flow in healthy subjects: effect of the rate of infusion

Abstract

Somatostatin is a naturally occurring peptide advocated for the management of hemodynamic complications of chronic liver diseases. The route of administration (bolus application or constant infusion) has been a question of debate. Our aim was to explore the effects of the somatostatin analog lanreotide, given as a bolus injection or continuous infusion, on food-stimulated hemodynamics in humans. Twelve healthy subjects (6 men and 6 women) were studied in a double-blind, double-dummy, randomized, crossover study. After a baseline period of 60 minutes, each subject received either a placebo bolus injection and an intravenous infusion of 100 microg/h lanreotide over a period of 8 hours or a placebo infusion over a period of 8 hours and an 800-microg lanreotide bolus injection. Simultaneously, a liquid test meal (Ensure Plus, 6.3 kJ/mL; Abbott Laboratories, Abbott Park, Ill) was perfused intraduodenally at 3 mL/min over a period of 8 hours. Diastolic blood pressure, heart rate, and superior mesenteric arterial and portal venous volume flows were measured at regular intervals by use of echo-Doppler technology. Plasma lanreotide levels were determined at defined intervals. Lanreotide as a 100-microg/h infusion for 8 hours was bioequivalent with lanreotide as an 800-microg bolus injection (mean area under the plasma concentration-time curve [AUC] extrapolated to infinity [AUC( infinity )], 1844.3 ng.min/L versus 1971.0 ng.min/L; AUC(infinity) ratios, 0.99; confidence interval, 0.95-1.02), and clearance was identical (479.2 mL/min versus 413.4 mL/min, P >.05). As expected, significant differences were observed in maximum plasma concentrations (75.58 ng/mL versus 4.85 ng/mL, P <.001) after infusion and bolus injections, respectively. Lanreotide at 100 microg/h over a period of 8 hours was well tolerated and abolished food-stimulated splanchnic hyperemia in both the superior mesenteric artery and the portal vein (mean AUC above baseline values [AUC(ab)], 37.25 L/min.min and 0.51 L/min.min, respectively). In contrast, the same dose of lanreotide given as a bolus injection only temporarily blunted postprandial hyperemia (mean AUC(ab) for superior mesenteric artery, 251.4 L/min.min, P <.001; mean AUC(ab) for portal vein, 194.95 L/min.min, P <.001), and subjects had significantly more side effects. On the basis of tolerability and hemodynamic effects, an intravenous infusion of lanreotide seems superior to a bolus injection of the same dose.