The impact of continuous subcutaneous infusion of octreotide on gallstone formation in acromegalic patients.

Treatment of acromegaly with intermittent sc injections of octreotide is associated with an increased incidence of cholelithiasis. We investigated the incidence of gallstone formation, the occurrence of gallbladder disease, and the response of gallstones to ursodeoxycholic acid in 30 acromegalic patients who were treated with a continuous sc infusion of octreotide at doses between 200 and 800 micrograms/day for 3-70 months. Of the 30 patients, 28 had pretretment ultrasonography of the biliary tree performed, and all had frequent follow-ups. Nine patients underwent pre- and posttreatment bile sampling. No patient treated for less than 6 months and 18.5% of patients treated for more than 6 months developed new gallstones. No patient developed symptomatic cholelithiasis while receiving octreotide therapy. Of six patients who developed gallstones, four were treated with ursodeoxycholic acid, which dissolved all gallstones. One patient with gallstones experienced an episode of biliary colic when octreotide was withdrawn; however, no cholecystitis was found at subsequent cholecystectomy. Bile sampling showed that 8 (75%) of the 12 patients who were assessed demonstrated microcrystals, whereas in 3 (50%) of 6 patients who were closely analyzed thereafter, microcrystals disappeared once octreotide therapy was stopped. Our results show that continuous sc infusion octreotide therapy increases the incidence of cholelithiasis over normal values, as is the case with intermittent sc injections. Although higher octreotide levels are sustained with continuous sc infusion, this is not associated with an increased risk of gallstone formation compared with intermittent sc octreotide therapy.

Safety, tolerability, efficacy and plasma concentrations of tropisetron after administration at five dose levels to children receiving cancer chemotherapy.

In a double-blind, placebo-controlled, escalating dose study, 44 children receiving cancer chemotherapy of various degrees of emetogenicity were randomly allocated to once-daily treatment with tropisetron 0.05 mg/kg (6 patients), 0.10 mg/kg (5 patients), 0.20 mg/kg (6 patients), 0.33 mg/kg (6 patients), 0.50 mg/kg (6 patients) or placebo (15 patients). All doses of tropisetron were well tolerated; no tropisetron recipient discontinued treatment because of intolerance and no adverse effect could be plausibly correlated to tropisetron administration. Therapeutic plasma concentrations of tropisetron (> 3 ng/ml) were present for 9 h after administration of doses of 0.10 mg/kg or more. Tropisetron at doses of at least 0.20 mg/kg was significantly more effective in preventing vomiting than lower tropisetron doses or placebo, both in terms of treatment failure (> four vomits) (P = 0.015) and patient and investigator efficacy ratings (P = 0.04 for investigator rating; P = 0.035 for patient rating). Further comparative studies of the efficacy of tropisetron in chemotherapy-induced emesis in children are warranted.