The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects

Abstract

Aims: Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release.

Methods: Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured.

Results: After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment.

Conclusions: The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.

Figure 1

Median 24 h pH-profiles during subcutaneous infusion of placebo (a) or vapreotide (b) in 10 healthy volunteers.

Figure 2

pH-distribution-curve of vapreotide (— day 2, –– day 7) and placebo (day 2, ––– day 7) in 10 healthy volunteers.

Figure 3

Whisker box plots of 24 h pH-profiles after subcutaneous infusion of vapreotide or placebo in 10 healthy volunteers.

Figure 4

Postprandial gallbladder volume on day 2 (□) and 7 (•) during 1 week treatment with subcutaneous infusion of either a) placebo or b) vapreotide (1.5 mg day⁻¹) in 10 healthy volunteers. Data given as percent change of basal volume (mean±s.e.mean).

Figure 5

Mean (±s.e.mean) postprandial cholecystokinin concentration (pmol l⁻¹) on day 2 (□) and day 7 (•) during subcutaneous infusion of a) placebo or b) vapreotide in 10 healthy volunteers.