[Effect of ursodeoxycholic acid treatment on primary biliary cirrhosis].
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Bile Acids and Salts↗
Biomedical subjects
A Stiehl
Publications and source records attributed to A Stiehl.
[Treatment of primary sclerosing cholangitis with ursodeoxycholic acid].
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Cholangitis, Sclerosing↗
Pharmacokinetics of picumast dihydrochloride in patients with liver cirrhosis.
In a randomized parallel group design the pharmacokinetics of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) and its active metabolites M1 and M2 were studied after intravenous or oral administration of a single dose of 10 mg picumast dihydrochloride in two groups of 8 patients with liver cirrhosis. After intravenous administration, the terminal half-life of 65 h was about 4 times longer than in healthy subjects although the total body clearance of 87 ml/min was only 7.4% lower. The 3.6-fold increase in the steady-state volume of distribution (351 l) may be due to a higher uptake by the liver and other tissues and/or to a slower re-diffusion from these tissues into the circulation. Only negligible amounts of picumast dihydrochloride appeared in the urine. Picumast dihydrochloride is almost exclusively eliminated by hepatic metabolism. After oral administration peak concentrations were reached at 1.4 h; plasma elimination half-life was considerably longer (107 h), however, without being significantly different from i.v. administration. The two patient groups differed with respect to their drug metabolizing capacity, therefore the absolute biovailability could not be established. The maximum concentration of the metabolites was reached 1.4 to 3.4 h later than Cmax of the parent drug. As compared to healthy subjects the clearance of the metabolites appeared to the reduced to a greater extent than that of the parent compound, so that under steady-state conditions in patients with liver disease these active metabolites will contribute more to the overall therapeutic effect than in normal individuals. 10.4% to 12.8% of the dose were recovered from the urine als M1.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Plasma clearance of bile acids in the rat: hepatic uptake under physiological conditions without countertransport.
Studies in rats by others indicated that sulfobromophthalein (BSP), bilirubin and indocyanine green are taken up by the liver and can be transported back to plasma against the prevailing concentration gradient (= countertransport). The present in vivo study was designed to determine whether the bile acids cholic acid and taurocholic acid under physiological conditions undergo appreciable countertransport as has been suggested by experiments in isolated hepatocytes. Experiments with BSP (controls) showed that injections of unlabeled BSP into rats five minutes after the administration of radiolabeled BSP was followed by a release of radioactivity into plasma (BSP-countertransport). In contrast bile acid countertransport could not be demonstrated, no matter whether it was tested 1, 5 or 8 minutes after the administration of radiolabeled cholic- or taurocholic acid.
Animals↗
Ileal excretion of bile acids: comparison with biliary bile composition and effect of ursodeoxycholic acid treatment.
The amount of bile acid excreted via an ileostomy at the end of the ileum should give an estimate of the amount of bile acid transported to the colon. In the present study, 8 patients with ileostomies at the end of the ileum but without disease or resection of the small intestine excreted 1690 +/- 205 mumol/day (mean +/- SEM) of bile acids from the ileostomies. In comparison with duodenal bile, cholic acid was increased at the end of the ileum and chenodeoxycholic acid decreased; in addition, bile acid sulfates were increased and bile acid glucuronides were decreased. When ursodeoxycholic acid, a bile acid that decreases biliary cholesterol saturation and dissolves gallstones, was administered at a dose of 500 mg to each subject, 59% +/- 8% (mean +/- SEM) of this bile acid was excreted within 24 h from the ileostomies. It is apparent from these studies that absorption of ursodeoxycholic acid from the small intestine is slower than previously anticipated and involves the entire small intestine and probably also the colon.
Adult↗
Metabolic changes in healthy men using fat-modified diets. II. Composition of biliary lipids.
The composition of fasting gallbladder bile was investigated in a group of 14 healthy men both on their normal diets and on a low cholesterol diet containing less saturated and more polyunsaturated fat given twice for 4 weeks. These dietary changes caused a 21.6% reduction of total serum cholesterol levels. With the use of the fat-modified diet lithogenic indices of fasting gallbladder bile were not significantly changed despite increased relative concentrations of bile acids and decreased relative concentrations of phospholipids and cholesterol in bile. Thus, the experiment provided no evidence for an increased cholelithiasis risk in healthy men ingesting 'prudent diets'.
Adult↗
Prospective study on the distribution of Campylobacter pylori in unselected patients of an endoscopy unit in West Germany.
In recent years a series of publications predominantly from English speaking countries have reported on the colonization of the gastric epithelium with Campylobacter pylori in association with gastritis and ulcer disease. In this prospective study we investigated the distribution of Campylobacter pylori in unselected patients undergoing routine endoscopy at the Department of Gastroenterology of the University of Heidelberg. A total of 175 patients were included in the study. Campylobacter pylori could be demonstrated by microbiological and histological methods in 17% of patients with normal gastric mucosa, in 44% with chronic active gastritis and in 48% with stomach ulcer. In our series only 6/23 patients with duodenal ulcer were Campylobacter pylori positive. Additionally intragastric acidity and concentrations of total bile acids were correlated to the colonization of Campylobacter pylori. Bile acid concentrations were found significantly (p less than 0.001) lower in patients with gastritis when Campylobacter pylori was present. These data suggest an association of Campylobacter pylori with diseases of the stomach also in West Germany and a negative correlation of these organisms to enterogastric bile reflux.
Adult↗
[Prevalence of Gilbert's syndrome in Germany].
The prevalence of Gilbert's syndrome was studied in a randomized group of 1530 persons (785 men and 745 women, aged 20-40 years) living in the Heidelberg region of the Federal Republic of Germany. It was found to be present in 12.4% of men and 4.8% of women, i.e. a total of 8.6% for the entire group. In women the serum bilirubin level (mean 12.0 +/- 5.1 mumol/l) was significantly lower than in men (mean of 13.7 +/- 6.8 mumol/l; P less than 0.001). Analysing the frequency distribution of serum bilirubin revealed that patients with this syndrome do not constitute a population of its own, but rather form the upper end of the normative bilirubin distribution curve.
Adult↗
[Ambulatory long-term prevention of thromboembolism with low-molecular weight heparin].
Patients with severe bleeding complications and other side effects on conventional anticoagulants and strong indication for further anticoagulation were treated with a low molecular weight heparin fragment (Tedelparin). In this paper we report the experiences in 30 patients, who were anticoagulated 1-11 months with this compound. All patients injected themselves a dose ranging from 1 X 2,500 to 1 X 20,000 anti factor Xa units per day. Within 132 months of treatment one patient with good compliance developed thromboembolism. Four patients had bad compliance. Two of them experienced rethrombosis 1 and 8 weeks after starting therapy. Severe haemorrhages did not occur. Two patients had one minor bleeding complication each. Both patients developed several times per year severe haemorrhages with conventional anticoagulants. All excessive subcutaneous haematomas and indurations of the adipose tissue at the injection site of conventional heparin disappeared completely. Low molecular weight heparin can be regarded as an alternative anticoagulant in patients with severe bleeding and other complications on oral anticoagulants and conventional heparin.
Adult↗
[Composition of gallbladder and bile duct calculi].
The composition of gallbladder and bile duct stones removed at the time of cholecystectomy was analysed in a consecutive series of 45 patients. The type of stones at the two sites was similar in all but two patients. Cholesterol content differed by more than 20% in only six patients. Cholesterol stones were found in the gallbladder of 33 patients, in the bile duct of 36 patients (73 and 80%, respectively); mixed stones in eight and five patients, respectively (18 and 11%); brown-pigment stones in three patients each (7%); black-pigment stones in one patient each (2%). Bile duct stones overlooked during cholecystectomy are thus suitable for litholysis, e.g. by irrigation with monooctanoin, in the majority of cases.
Bile Duct Diseases↗
Gilbert's syndrome: diagnosis by typical serum bilirubin pattern.
Analysis of serum unconjugated and conjugated bilirubin fractions by routine diazo procedures does not allow a definite diagnosis of Gilbert's syndrome. By the alkaline methanolysis procedure of Blanckaert followed by thin-layer chromatography we were able to discriminate Gilbert's syndrome even in the presence of normal serum bilirubin concentrations from healthy subjects, patients with chronic persistant hepatitis and patients with chronic hemolysis. The relative proportion of unconjugated bilirubin in serum was 95 +/- 2% in patients with Gilbert's syndrome (n = 28), 84 +/- 5% in healthy subjects (n = 29), 75 +/- 6% in patients with chronic persistant hepatitis (n = 7) and 85 +/- 3% in patients with chronic hemolysis (n = 9). The difference between Gilbert's syndrome and the control groups with normal or elevated serum bilirubin was highly significant (p less than 0.001). In Gilbert's syndrome, unconjugated bilirubin ranged between 90 and 99%, in healthy subjects between 72 and 90%, in patients with chronic persistant hepatitis between 68 and 85% and in patients with chronic hemolysis between 81 and 89% of total. An overlap was only seen in one patient with Gilbert's syndrome and in 2 healthy subjects at the 90% level. We conclude that in most patients with Gilbert's syndrome provocation tests are no longer necessary.
Adolescent↗
Isomers of bilirubin glucuronide in serum and bile before and after relief of common duct obstruction.
Isomers of bilirubin glucuronide with the bilirubin acyl group attached to the C1-, C2-, C3- and C4-positions of the glucuronyl residue are present in bile of patients with extrahepatic cholestasis, whereas in normal bile only C1-isomers are found. In the present study, these bilirubin glucuronide isomers, and the fractions of unconjugated bilirubin, and bilirubin mono- and diconjugates were determined in serum and bile of 8 patients before and after relief of common duct obstruction by endoscopic papillotomy. Before papillotomy we found 39.6% C1-isomers (median value), 22.2% C2-isomers, 19.3% C3-isomers and 11.4% C4-isomers in the bile. The values in serum before papillotomy were comparable. Twenty-four hours after papillotomy, the level of C1-isomers in bile increased significantly to 56.3% (P less than 0.05) with a concomitant decrease of the non-C1-isomers. In contrast, in serum the isomers of bilirubin glucuronide did not change significantly at 24 h after papillotomy. Before papillotomy, the fraction of unconjugated bilirubin in bile was 3.6% of the total, with 15.8% bilirubin monoconjugates and 75.5% bilirubin disconjugates. After papillotomy, unconjugated bilirubin decreased to 1.6% (n.s.) and bilirubin monoconjugates to 11.9% (n.s.), while bilirubin diconjugates increased to 86.1% (P less than 0.05). In serum, the elevated fractions of bilirubin diconjugates and monoconjugates decreased from 38.4 to 32.2% (P less than 0.05) and from 29.6 to 23.4% (n.s.), respectively. In parallel, the fraction of unconjugated bilirubin in serum increased from 24.1 to 37.0% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Colonic absorption of sulfated and nonsulfated bile acids in rat.
Absorption of sulfated and nonsulfated chenodeoxycholic and glycochenodeoxycholic acid was studied in the colon and the data were compared with the absorption rates in the ileum. Absorption of nonsulfated chenodeoxycholic acid in the colon was in the same range of magnitude as in the ileum. Glycochenodeoxycholic acid absorption in the colon was lower than in the terminal ileum. Sulfated bile acids were not absorbed in the colon. In the ileum, absorption of sulfated bile acids was significantly (p less than 0.01) lower than the absorption of nonsulfated bile acids. Little absorption of sulfated bile acids in the ileum and lack of absorption in the colon both contribute to the rapid turnover and excretion of bile acid sulfates.
Animals↗
Pharmacokinetics of ceftizoxime.
The kinetics of ceftizoxime, a newly developed cephalosporin, were evaluated in 6 healthy subjects, with respect to its excretory pathways especially by the biliary route. Total, renal and biliary clearance were determined at two different steady states. Steady state was achieved by constant intravenous infusion (604.1 mg/h) over 6 h after an initial loading dose (750 mg); 1.5 h after discontinuation of that infusion, a further infusion was commenced at a lower rate (284 mg/h) over 3 h, the second steady state being reached 0.5 to 1.0 h later. The drug was mainly excreted by the kidneys (56.7 to 92.9% of the dose). Biliary excretion, measured by the duodenal perfusion and marker dilution technique, was low (0.2 to 7.8% of the dose). Urinary and biliary excretion as well as total clearance were not dose-dependent. However, there was pronounced interindividual variation in total (35.2 to 236 ml/min) and renal clearance (10.6 to 208 ml/min), which could both be explained by varying interindividual urinary flow rates (mean flow rate: 0.99 ml/min to 3.14 ml/min). Intraindividual variation in renal clearance was less pronounced, but in the same subject changes in renal clearance were correlated with changes in urinary flow rate. From the varying renal clearance, which exceeded the glomerular filtration rate at high urinary flow rates and was below it at low urinary flow rates, it can be concluded that, in addition to glomerular filtration, tubular secretion and tubular reabsorption are involved in the renal excretion of ceftizoxime.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Absorption of urso- and chenodeoxycholic acid and their taurine and glycine conjugates in rat jejunum, ileum, and colon.
Chenodeoxycholic acid (cheno) and ursodeoxycholic acid (urso) dissolve cholesterol gallstones in man. Comparative studies of the absorption of cheno and urso are not available. The absorption of urso and cheno and their glycine and taurine conjugates in jejunum, terminal ileum, and colon of the rat were therefore determined in an open in situ perfusion system. Absorption of unconjugated urso and cheno in jejunum, ileum, and colon was similar. In the jejunum conjugated urso and cheno were absorbed only in minimal amounts. In the ileum glycine-conjugated urso was absorbed to a lower extent than glycine-conjugated cheno (6.5 +/- 0.4 vs. 8.6 +/- 0.6 nmol/cm X h at 25 mumol/l bile acid concentration, p less than 0.05) and taurine-conjugated urso was absorbed less than taurine-conjugated cheno (6.4 +/- 0.5 vs. 8.1 +/- 0.7 nmol/cm X h, p less than 0.05). In the colon glycourso and taurourso were not absorbed, while glycocheno and taurocheno were absorbed in small amounts. The low reabsorption rates of urso conjugates in ileum and colon may contribute to the relatively low urso content in bile during urso treatment.
Animals↗
Absorption of 7-ketolithocholic acid in rat jejunum, ileum and colon.
7-Ketolithocholic acid is a bile acid which is formed in the intestine of man by bacterial oxidation of chenodeoxycholic acid and ursodeoxycholic acid. In contrast to deoxycholic acid and lithocholic acid 7-ketolithocholic acid after its intestinal absorption may be reduced in the liver to chenodeoxycholic acid or ursodeoxycholic acid. In the present study absorption of 7-ketolithocholic acid in jejunum, ileum, and colon was measured. When 7-ketolithocholic acid was perfused with a concentration of 0.025 mmol/l the absorption in the jejunum was 6.2 +/- 0.9 nmol/cmxh (mean +/- SD), in the ileum 8.1 +/- 0.2 nmol/cmxh, and in the colon 11.2 +/- 1.7 nmol/cmxh. The absorption of 7-ketolithocholic acid in jejunum, ileum, and colon was equal to the absorption of ursodeoxycholic and chenodeoxycholic acid. The equal absorption rates of 7-ketolithocholic, ursodeoxycholic, and chenodeoxycholic acid indicate, that substitution of the 7-hydroxyl group by the 7-keto group has no influence on the intestinal absorption of bile acids. The excellent colonic absorption of 7-ketolithocholic acid demonstrates, that not only the small intestine but also the colon contributes to the enterohepatic circulation of bile acids.
Animals↗
Intestinal absorption of levodopa in man.
In four healthy subjects the intestinal absorption of levodopa (l-dopa) was investigated by measuring the plasma concentration of the amino acid following the administration of l-dopa at three different sites in the small intestine. In order to minimize presystemic clearance of l-dopa, the subjects were pretreated with the peripheral decarboxylase inhibitor benserazide 3 X 50 mg every 8 h on the previous day and 1 X 50 mg 2 h prior to administration of the l-dopa. L-dopa 100 mg dissolved in 0.05 N HCl and 50 mg benserazide dissolved in 0.05 N HCl were coadministered. Under these conditions no difference in tmax, cmax or AUC of l-dopa was observed between administration of the drug into the proximal or the distal part of duodenum, or into the upper part of jejunum. The results indicate that in healthy subjects, during inhibition of peripheral decarboxylase, the rate and extent of l-dopa absorption does not differ at any site in the upper small intestine.
Adult↗
Nonlinear mezlocillin kinetics due to dose-dependent metabolism.
Dose-dependent kinetics of intravenous bolus-dose mezlocillin, a newly developed ureidopenicillin, have been reported by several investigators. In eight healthy subjects we examined renal, biliary, and total clearance at different steady-state levels. After infusion of doses of 22.4 +/- 1.5, 11.4 +/- 0.7, and 5.6 +/- 0.4 mg/min mean plasma steady-state levels of 88.4 +/- 15.9, 40.3 +/- 7.5, and 18.4 +/- 4.6 micrograms/ml were achieved. Metabolic clearance was estimated as the difference between total clearance and the sum of renal and biliary clearance, assuming that no other route of excretion plays an important role in the elimination of the drug. Total clearance varied between 355.7 +/- 59.3 and 286.5 +/- 54.6 ml/min when doses of 5.6 +/- 0.4 and 22.4 +/- 1.5 mg/min were given. Since neither renal clearance (137.6 +/- 32.6 ml/min) nor biliary clearance (98.6 +/- 42.5 ml/min) was shown to be dose dependent, nonlinear mezlocillin kinetics must be due to dose dependent metabolic clearance (108.4 +/- 26.2 versus 60.2 +/- 32.3 ml/min at 5.6 +/- 0.4 and 22.4 +/- 1.5 mg/min). The apparent Km was 27.5 micrograms/ml and apparent Vmax 4.3 mg/min. The apparent Km is so low that after therapeutic doses of mezlocillin the kinetics are nonlinear for several hours.
Adult↗