Dose-response effects of oral loxiglumide on postprandial gall-bladder emptying in man.

The effect of two different single oral doses of loxiglumide (CR 1505, CAS 107097-80-3) on gall-bladder emptying induced by a 550-cal standard mixed meal in 6 healthy volunteers was studied. Following placebo, the maximal gall-bladder emptying occurred about 90 min after the meal (minimal residual gall-bladder volume 27.4% of basal volume). Loxiglumide 400 or 800 mg dose-dependently inhibited the physiologica gall-bladder emptying. Loxiglumide plasma levels dose-dependently increased. The inhibition of gall-bladder emptying and the kinetic of loxiglumide plasma levels were temporally related. The results of the present study confirm that oral loxiglumide is a potent orally active cholecystokinin (CCK) antagonist in man and that CCK is the major physiological mediator of gallbladder emptying in response to meal.

Effect of loxiglumide on gallbladder contractile response to cerulein and food in humans.

The present study investigated the effect of loxiglumide, a new selective cholecystokinin-receptor antagonist, on the gallbladder contractile responses to caerulein and to food in humans. In 6 healthy men, the gallbladder emptying driven by intravenous infusion of stepwise increasing doses of cerulein (10-80 ng/kg . h) and that induced by a 550-cal standard meal were monitored by ultrasonography. In both sets of experiments, the effect of loxiglumide was tested at various infusional rates against a control infusion of saline. An infusional rate of 2.5 mg/kg . h of loxiglumide abolished the gallbladder response even to maximal doses of cerulein, whereas a rate of 1.0 mg/kg . h counteracted the cholecystokinetic activity of cerulein up to the dose of 20 ng/kg . h. In postprandial experiments, the cholecystokinin antagonist dose-dependently inhibited the physiologic gallbladder contraction. The maximal gallbladder emptying, which always occurred 85 min after the meal, was 71.1% +/- 3.3% of basal volume in control studies, 39.2% +/- 1.8% during infusion of 2.5 mg/kg . h of loxiglumide, and 17.3% +/- 5.9% when 5.0 mg/kg . h were infused. A dose of 7.5 mg/kg . h of loxiglumide was able to prevent any postprandial emptying of the gallbladder. The present study shows that a selective cholecystokinin receptorial blockade competitively antagonizes cerulein-induced gallbladder contraction and dose-dependently inhibits postprandial gallbladder emptying.

Ultrasound-assisted percutaneous liver biopsy: superiority of the Tru-Cut over the Menghini needle for diagnosis of cirrhosis.

A total of 1192 consecutive patients with diffuse liver disease were randomized to have percutaneous liver biopsy specimens taken with the Menghini or the Tru-Cut needle, to compare tissue yield, safety, and accuracy of the two needles for diagnosing cirrhosis. The sites of puncture were determined by prebiopsy ultrasound scans. Adequate samples were obtained from 94% with the Tru-Cut needle and from 79.2% with the Menghini needle (p less than 0.001). Accuracy in diagnosing cirrhosis was 89.5% for the Tru-Cut needle and 65.5% for the Menghini needle (p less than 0.05). Complication rates were very low and similar for both needles. Under these conditions, the Tru-Cut needle is superior to the Menghini needle for diagnosing cirrhosis.

A combination of chenodeoxycholic acid and ursodeoxycholic acid is more effective than either alone in reducing biliary cholesterol saturation.

The effects on biliary lipids of 10 mg per kg per day of chenodeoxycholic acid (CDCA), 10 mg per kg per day of ursodeoxycholic acid (UDCA), and their equimolar combination (5 mg per kg per day of each), all administered for 45 to 60 days, were investigated in 18 patients with gallstones in a double-blind study with a balanced latin square design. The molar percentage of cholesterol in bile (initial value 9.7 +/- 2.2) was significantly lower after UDCA (5.4 +/- 1.3) and the combination (5.2 +/- 1.2) than after CDCA (7.2 +/- 1.7). Nevertheless, when the ability to solubilize cholesterol was calculated, taking into account the percentage of biliary UDCA, then the differences in cholesterol saturation induced by UDCA alone and the combination also became considerable (saturation index: 0.94 +/- 0.12 as compared to 0.81 +/- 0.12). The total bile acid pool increased significantly after treatment with CDCA and the combination, but not after UDCA. Lithocholic acid was increased significantly only by treatment with CDCA. Diarrhea was observed in five patients with hypertransaminasemia and in four patients after CDCA, whereas both UDCA and the combination were well-tolerated. We conclude that the administration of a combination of equimolar doses of CDCA and UDCA can be recommended for medical treatment of gallstones since it has greater effects on bile cholesterol saturation than either alone, is better tolerated than CDCA, and is less expensive than UDCA.

Effect of dihydroxydibutylether (DHBE) on bile flow and composition in rats with ethynylestradiol-induced cholestasis.

Administration of dihydroxydibutylether (DHBE, Dis-Cinil) to rats with ethynylestradiol(EE)-induced cholestasis provoked an increase in bile flow and output of bile acids and phospholipids. Since EE-induced cholestasis is related to the condition observed in humans, a clinical trial of DHBE in cholestatic syndromes seems worthwhile.