Diminishing efficacy of octreotide (SMS 201-995) on gastric functions of healthy subjects during one-week administration.
In this study, the pharmacokinetics, efficacy, and tolerability of 25 and 100 micrograms of octreotide given t.i.d. for 7 days subcutaneously were investigated in 12 healthy male subjects. Serum concentrations of the drug were well reproducible within 1 wk. Octreotide significantly raised 24-h median intragastric pH on day 1, but no longer on day 6. Peptone-stimulated gastric acid and volume secretion were markedly less suppressed by octreotide on day 7 compared with day 2. Peptone-stimulated gastrin release was abolished on days 2 and 7, as was peptone-stimulated insulin release. Blood glucose was altered in a biphasic pattern on days 2 and 7. All effects of octreotide were without clear-cut dose-response relationship. A mean half-life of 115 min was calculated. Dose-unrelated side effects (e.g., abdominal cramps, diarrhea, and fatty stools) were registered. In conclusion, octreotide is a powerful inhibitor of gastric acid and volume secretion during acute treatment. Its loss of efficacy during a 1-wk administration may be due to the adaptation of somatostatin receptors and hormonal counterregulation.
Londong
W
W
Medizinische Klinik Innenstadt, University of Munich, Federal Republic of Germany.
Angerer
M
M
Kutz
K
K
Landgraf
R
R
Londong
V
V
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D015282:Octreotide / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011897:Random Allocation; D013997:Time Factors
D001786:Blood Glucose; D005755:Gastrins; D015282:Octreotide