GASTROENTEROLOGY

Intestinal Absorption of Ursodeoxycholic in Patients With Extrahepatic Biliary Obstruction and Bile Drainage SIEGFRIED WALKER, and ADOLF STIEHL

GERDA

RUDOLPH,

Deuartment of Gastroenterolonv. Robert-Bosch-Krankenhaus, University of Heidelberg, Heidelberg, Germany Y_

Ursodeoxycholic acid (UDCA) dissolves cholesterol gallstones and improves liver function test results in patients with cholestatic liver diseases. Its absorption was studied in patients who had complete extrahepatic biliary obstruction caused by pancreatic carcinoma but no intestinal or liver disease. Six patients received 500 mg chenodeoxycholic acid (CDCA) or 250-2000 mg UDCA in capsules in single oral doses in random order, with an interval of 2 days between the different treatment regimens. In the control period the patients excreted into bile 382.3 t 108.0 pmol CDCA (mean + SD) and 1866.7 k 172.6 pmol cholic acid per 24 hours. After administration of 1273.6 pmol (500 mg) CDCA, biliary excretion of this bile acid increased to 1370.9 k 185.7 pmo1/24 h, indicating an intestinal absorption rate of 77.6% + 9.8%. After oral administration of 636.8 pmol (250 mg), 1273.6 pmol (500 mg), 2547.2 pmol (1000 mg), and 5094.4 pmol(2000 mg) of UDCA, the respective absorption rates were 60.3% 1- 7.4%, 47.7% + 9.0%, 30.7% f 7.5%, and 20.8% + 3.9%, and whereas in the control period no UDCA was detected in the bile, the UDCA percentages measured were 14.6% + 8.2%, 19.6% + 9.1%, 23.1% f 11.3%, and 27.4% f 12.1%. The coadministration of CDCA did not enhance the absorption of UDCA. The data indicate that absorption of orally administered CDCA is almost complete, whereas UDCA absorption is incomplete. With increasing doses UDCA absorption decreases. To achieve absorption of adequate amounts of UDCA, high and/or multiple doses are needed. rsodeoxycholic acid (UDCA) is used for the dissolution of cholesterol gallstones’*’ and may have beneficial effects in cholestatic liver diseases such as primary biliary cirrhosis3 and primary scleStudies in patients with ileosrosing cholangitise4 intestinal absorption of tomy5v6 suggest incomplete UDCA after oral administration. Because patients with ileostomy involving the distal end of the ileum

U

RICHARD

1992:102:810-815

Acid

RAEDSCH,

Stuttgart; and Department of Gastroenterology,

lack the ileocecal valve, the amount of absorption may be underestimated. In view of this, absorption was studied in patients who had complete extrahepatic biliary obstruction caused by pancreatic carcinoma but no intestinal or liver disease. Advantages of this method are complete collection of bile and the possibility of measuring the intestinal absorption quantitatively.

Materials and Methods Six patients with tumors of the head of the pancreas leading to complete extrahepatic bile duct obstruction were included. Table 1 shows the clinical data of the patients before biliary drainage and at entry into the study. In none of the patients had relief of cholestasis by endoscopic means been possible. Therefore, an external 7F biliary drainage catheter was inserted under fluoroscopic control. Complete obstruction of the distal bile duct was documented by percutaneous transhepatic cholangiography. Only patients with no indication of liver or intestinal disease and in whom cholestasis had almost completely disappeared, as indicated by serum bilirubin and alkaline phosphatase levels, were included. The study was started 5-7 days after the drainage procedure. Study

Design

UDCA and chenodeoxycholic acid (CDCA; Ursofalk and Chenofalk capsules; provided by Dr. H. Falk, Freiburg, Germany) were given orally at 8 AM before breakfast. The patients were on a normal hospital diet. All the bile secreted was collected in a closed system, withdrawn from the collecting bag every 2 hours, and stored at -20°C. In two patients (patients 1 and 2), bile was collected and analyzed hourly for 8 hours after the administration of two capsules of UDCA. Because biliary secretion in patients with previous cholestasis may be somewhat delayed, the pooled 24-hour bile samples were analyzed. One, 2,4, or 8 capsules of UDCA or 2 capsules of CDCA containing 636.8 Frnol (250 mg) each in a single dose were administered to six patients (patients l-6)in random order 0 1992 by the American Gastroenterological Association 0016-5085/92/$3.00

URSODEOXYCHOLIC ACID ABSORPTION 811

March 1992

Table 1. Data of Patients

With Complete Extrahepatic

Biliary Obstruction

Before Drainage

Alkaline phosphataseb

Bilirubin” Patient no. 1 2 3 4 5 6

M/F

Age (yr)

Weight (kg)

M F F F F M

68 77 61 63 70 51

73 66 58 59 65 61

Before drainage

Study entry

Before drainage

51.0 22.1 54.4 54.4 49.3 35.7

302.6 132.6 408.0 246.5 324.7 368.9

and at Entry Into the Study

Study entry

1340 627 845 890 2051 1407

201 182 248 376 541 309

NOTE. Absorption of 500 mg CDCA and UDCA in doses ranging from 250 to 2000 mg was studied. In addition, in patients l-5,the effect of 500 mg CDCA on the absorption of 500 mg UDCA was studied. “Bilirubin level in pmol/L (normal c20.4). bAlkaline phosphatase in U/L (normal ~170).

with an interval of at least 2 days between the different study periods. In addition, five patients_(patients l-5) received two capsules each of UDCA and CDCA, and the absorption of UDCA was compared with that of UDCA when given alone. Bile and 24-hour urine samples were analyzed as described earlier.7 After solvolysis of bile acid sulfates and hydrolysis of bile acid glucuronides by glucuronidase, the bile acids were separated on DEAP-LH 20 (Packard International, Zurich, Switzerland) into nonamidated bile acids, taurine conjugates, and glycine conjugates.’ Alkaline hydrolysis” was used to deamidate taurine and glycine conjugates. Gas-liquid chromatography of methylated and trimethylsilyl-substituted bile acid derivatives was performed on 4.5-m 0.5% HiEff 8BP (Applied Science Laboratories Inc., State College, PA) conventional glass columns and on 50-m OV 101 (Marcherey und Nagel, Diiren, Germany) glass capillary columns. An HP 5710A gas chromatograph (Hewlett Packard, Bad Homburg, Germany) equipped with a flame ionization detector was used. Intestinal absorption of CDCA was estimated from the biliary secretion of the orally administered bile acid minus the secretion of the respective bile acid during the control period. The study was approved by the ethics committee of the institution. Informed consent was obtained in all patients. The Wilcoxon matched pairs signed rank test and, for statistical comparison of the different UDCA dose groups, nonparametrical variance analysis according to Wilcoxon and Wilcox were used.g,‘o Results are given as means + SD.

were almost completely

conjugated with glycine and taurine. During the 24 hours, the following amounts were recovered from the bile: 384.1 + 47.1 lmol of the administered 636.8 pmol UDCA (250 mg), 607.5 + 114.6 pmol of the 1273.6 pmol UDCA, 780.9 + 191.0 pmol of the 2547.2 pmol UDCA, and 1059.6 + 198.7 pmol of the 5094.4 pmol UDCA. Less than 0.5% of the dose administered was found in the urine. The percentage of absorption at the various UDCA doses is shown in Table 2 and is significantly different at the 5% level between 250 and 1000 mg and between 500 and 2000 mg and at the 1% level between 250 and 2000 mg. After administration of 1273.6 pmol CDCA (500 mg), biliary excretion of this bile acid increased from 382.3 f 108.0 to 1370.9 f 185.7 ymo1/24 h, indicating an intestinal absorption of 988.6 + 124.8 pmol of the 1273.6 pmol CDCA taken orally. Thus, the absorption rate of 1273.6 ymol (500 mg) UDCA is significantly lower than that of 1273.6 pmol CDCA (47.7% Z!I9.0% vs. 77.6% f 9.8%; P < 0.05). When 1273.6 ymol CDCA and 1273.6 bmol UDCA

Results During the control periods the patients secreted 603.6 + 170 mL bile per 24 hours containing 2249 f 17% + The in two

647 pmol bile acids (83% * 8.0% cholic acid, 4.8% CDCA, and no UDCA). time course of the UDCA absorption was slow patients (Figure 1).

Total bile acid secretion and the excretion of cholit acid, CDCA, and UDCA during the control period and after the administration of different doses of UDCA are shown in Figure 2. All biliary bile acids

4

0

2

4

6 Time,

8

24

.

40

hr

Figure 1. Time course of the intestinal (pmol/h) after the administration of two patients with complete extrahepatic bile external biliary drainage. - ??-, Patient

absorption of UDCA capsules of UDCA in duct obstruction and I; - A -, patient 2.

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WALKER ET AL.

GASTROENTEROLOGY Vol. 102, No. 3

:

_

80

-

‘G

T

1

i

1 Y

.p

~_________-”

.=.:&.=.1.z.-_._._.-.-.-.____._._._p I

1000

1500

e

60-

s 2

40-

5

20-

4

o. Administered

z m

UDCA

Dose,

were coadministered, the absorption of UDCA was not significantly changed compared with that obtained when UDCA was administered alone. The absorption of UDCA in the individual five patients is shown in Figure 3. In Figure 4 the percentages of UDCA, cholic acid, and CDCA in bile are shown in the control period and after oral intake of one, two, four, and eight capsules containing 638.8 umol of UDCA. At a dose > 1273.6 ymol, the UDCA content in bile increased only slightly. Other bile acids, including 7-ketolithocholic acid, were not detected. Bile volume in the control period and after the oral intake of 1, 2,4, and 8 capsules of UDCA is shown in Figure 5. In all patients, bile flow increased with increasing dose. Discussion In patients with extrahepatic biliary obstruction and external bile fistula, biliary secretion of bile

Bile

Acid,

Dose

500

mg

Figure 3. Absorption of UDCA in five patients after 500 mg UDCA or 500 mg CDCA and 500 mg UDCA was not significantly different.

acids represents maximally stimulated bile acid synthesis.” In such patients the intestinal absorption of orally administered bile acids may be studied. In our patients the biliary secretion of endogenous bile acids in the control phase was constant. Because UDCA, in contrast to cholic acid, CDCA, and deoxycholic acid, does not suppress primary bile acid biosynthesis,12v’3 the biliary excretion of endogenous bile acids in our patients receiving UDCA is equal to the maximally stimulated bile acids synthesis. In bile samples collected on days when no UDCA was administered, no UDCA was detected, indicating that its absorption was completed within 1 day and that accumulation did not occur. Because no UDCA was secreted in the control phase, in the case of UDCA, the intestinal absorption was equivalent to the biliary secretion. In the present study involving patients with tumor obstruction of the bile duct and external drainage, the intestinal absorption of UDCA was shown to be incomplete and to decrease with increasing dose. The coadministration of CDCA did not enhance the absorption of UDCA. It appears possible that im-

Table 2. Percentage of Absorption of UDCA After Oral Intake of I, 2,4, and 8 Capsules Containing 250 mg UDCA UDCA dose

UDCA+CDCA

mg

Figure 2. Total bile acid secretion (- ??-) and cbolic acid ( * *V * - ), CDCA (- 0 -_), and UDCA (- A -_) secretion in the control period and after the oral intake of 1,2,4,and 8 capsules of UDCA in patients with complete extrahepatic bile duct obstruction and external biliary drainage.

[pmol

100 80

[mg)] i#

Patient no.

636.6

1273.6

(250)

(500)

2547.2 (1000)

1 2 3 4 5 6

46.8 59.4 63.5 62.8 68.6 60.3 60.3 7.4

38.3 38.4 47.2 52.8 62.1 47.4 47.7 9.0

18.0 32.7 32.2 41.3 29.1 30.9 30.7 7.5

Mean SD

UDCA

2000

al

5094.4

(2000) 14.7 19.5 21.3 26.9 20.7 21.7 20.8 3.9

-.

-. pT “--CL--_______ 1

60

p____ --------em_-____

-c

40 20

__~~~~____________________~

t

oL/ 0

.

I

1000

600

UDCA

dose,

1600

2000

mg

Figure 4. Percentage of UDCA (- A -), cholic acid (- V -), and CDCA (- 0 -) in the bile is shown in the control period and after the oral intake of 1,2,4, and 8 capsules of UDCA.

LJRSODEOXYCHOLIC

March 1992

UDCA Dose, mg Figure 5. Bile flow in the control period and after the oral intake of 1, 2, 4, and 8 capsules of UDCA in patients with complete extrahepatic bile duct obstruction and external biliary drainage.

proved solubilization of UDCA may be counteracted by competitive inhibition of its absorption. Complete obstruction of the distal bile duct was documented by percutaneous transhepatic cholangiography when the external biliary drainage catheter was implanted. The lack of deoxycholic acid in the bile is a result of the absence of cholic acid from the intestine. An effect of bile acid and pancreatic juice deficiency on the bile acid absorption cannot be excluded. However, the close agreement with the results obtained in patients with ileostoma4p5 without biliary obstruction and normal pancreatic exocrine function suggests that this effect can be expected to be small. The fractional hepatic extraction of unconjugated UDCA is lower than that of unconjugated CDCA.‘* Because the urinary excretion of both bile acids was minimal and the increase was very similar, differences in the hepatic uptake cannot explain the different biliary secretion rates of UDCA and CDCA in our patients. Bioavailability studies in humans’5-‘8 and perfusion studies in ratslg showed comparable absorption rates for UDCA16p’8and CDCA’5*‘7 in aqueous solution. In patients with ileostomies involving the distal end of the ileum, the excretion of UDCA was 59% + 8% after oral administration of 500 mg of UDCA.5 This is in good agreement with the absorption rate of 47.7% f 9.0% in the present study, considering that some unconjugated UDCA may be absorbed in the colon. The absorption rate decreased with increasing UDCA dose. This could be caused by saturation of the active transport sites in the terminal ileum20*21 but may also be a result of the decreasing solubility in water with increasing dose of UDCA. A similar tendency has been observed in studies on the absorption of CDCA in which, at very high doses, ab-

ACID ABSORPTION

813

sorption of CDCA also has been shown to be relatively decreased02’ In the rat, at pH 8.0 when UDCA is in solution, passive absorption of UDCA is as effective as the absorption of CDCA,lg whereas at pH 7.323 it was slower. Passive transport by diffusion increases linearly with the bile acid concentration in the solution. UDCA gets into solution very slowly because of the stability of the crystal lattice. Because UDCA solubilization is slow and pH dependent, and the pH throughout the length of the intestine is mostly below 8, the low solubility of UDCA at physiological intestinal pH24 may be the most important factor for ineffective intestinal absorption and low biliary UDCA content in UDCA-treated patients.25-27 The slow absorption of UDCA, as confirmed in the current study, may lead to competitive inhibition of the absorption of endogenous bile acids.5,28 Because the orocecal transit time on average ranges from 3 to 7 hours, it may be assumed that some UDCA may be absorbed from the colon. Recently it has been shown that in addition to the regulation of bile acid synthesis in the liver, there may be a second site of regulation in the enterocytes.2g In these experiments it was shown that in bile acid-depleted guinea pig and rat, intestinal bile acid absorption was maximally stimulated.2g Accordingly, in patients with extrahepatic obstruction and external biliary drainage, absorption can be expected to be increased. This would lead to some overestimation of the bile acid absorption in such patients. In UDCA-treated patients with intact enterohepatic circulation, biliary-secreted UDCA is not lost, and recirculating UDCA conjugates lead to a higher UDCA content in the bile26 than seen in the present study. However, the reduced absorption of conjugated UDCA as compared with conjugated CDCA” may also contribute to the lower UDCA content in the bile of UDCA-treated patients.25-27 Bacterial degradation of UDCA to 7-ketolithocholic acid30e3’cannot explain this difference, because 7-ketolithocholit acid was not detected in ileal fluid;5 in addition, this keto bile acid may be absorbed from the colon.33 After CDCA administration, no 7-ketolithocholic acid and UDCA were detected in bile; vice versa, after UDCA administration, no 7-ketolithocholic was in bile and CDCA excretion did not increase (Figure 2). Therefore, the data argue against substantial conversion of CDCA to UDCA or UDCA to CDCA in the patients studied. Besides the limited absorption of UDCA, the maximum hepatic synthesis of the primary bile acids cholit acid and CDCA will also contribute to the low relative content of UDCA in the bile of our patients. Bile flow increased with UDCA dose in each of the

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WALKER ET AL.

patients. Because the patients received UDCA in single doses and not by constant infusions, we do not believe that the experimental setup permits conclusions to be drawn concerning the presence or absence of UDCA-induced hypercholeresis.34*35 In agreement with previous studies, the absorption of orally administered CDCA is almost complete,15*17 whereas UDCA absorption is not. With increasing doses UDCA absorption decreases. It is concluded that to achieve absorption of adequate amounts of UDCA, high doses and/or multiple doses are needed. We suggest that when used in patients with hepatobiliary diseases, UDCA should not be administered in single doses as suggested for CDCA3” but preferably in a number of small doses distributed throughout the day. References 1. Makino I, Shinozaka

K, Yoshino K, Nakagawa S. Dissolution of cholesterol gallstones by ursodeoxycholic acid. Jpn J Gastroenterol 1975;72:690-702. 2. Bachrach WH, Hofmann AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Dig Dis Sci 1982; 27:737-761.833-856.

3. Poupon R, Chretien Y, Poupon RE, Ballet F, Calmus Y, Darnis F. Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? Lancet 1987;2:834-836. 4. Stiehl A, Raedsch R, Kommerell B. The effect of ursodeoxycholic acid (Urso) in primary sclerosing cholangitis. A comparison to primary biliary cirrhosis (abstr). Gastroenterology

14. Hofmann

AF. Bile acids. In: Arias IM, Jakoby WB, Popper H, Schachter D, Shafritz DA, eds. The liver: biology and pathobiology. New York: Raven, 1968:553-572. 15. Van Berge-Henegouwen GP, Hofmann AF. Pharmacology of chenodeoxycholic acid. II. Absorption and metabolism. Gastroenterology 1977;73:300-309, 16. Matern S, Tietjen KG, Fackler 0, Hinger K, Herz R, Gerok W. Bioavailability of ursodeoxycholic acid in man: studies with a radioimmunoassay for ursodeoxycholic acid. In: Paumgartner G, Stiehl A, Gerok W, eds. Biological effects of bile acids. Lancaster, England: MTP Press, 1979:109-118. 17. Ponz de Leon M, Loria P, Carulli N, Murphy GM, Dowling RH. Intestinal solubilization, absorption, pharmacokinetics and bioavailability of chenodeoxycholic acid. Eur J Clin Invest 1980;10:261-271, 18. Parquet

M, Metman EH, Raizman A, Rambaud JC, Berthaux N, Infante R. Bioavailability, gastrointestinal transit, solubilization and fecal excretion of ursodeoxycholic acid in man. Eur J Clin Invest 1985;15:171-178. 19. Walker S, Stiehl A, Raedsch R, Kloters P, Kommerell B. Absorption of urso- and chenodeoxycholic acid and their taurine and glycine conjugates in rat jejunum, ileum and colon. Digestion 1985;32:47-52. 20. Krag E, Phillips SF. Active and passive bile acid absorption in man. Perfusion studies of the ileum and jejunum. J Clin Invest 1974;53:1686-1694. 21. Lack L. Mechanisms

of ileal bile salt transport: implications drawn from structure-activity studies. In: Paumgartner G, Stiehl A, Gerok W, eds. Enterohepatic circulation of bile acids and sterol metabolism. Lancaster, England: MTP Press, 1965:243-247.

22. Danzinger

1988;94:A595. 5. Stiehl A, Raedsch R, Rudolph

G. Ileal excretion of bile acids: comparison with biliary bile composition and effect of ursodeoxycholic acid treatment. Gastroenterology 1988;94:1201-

1206. 6. Stiehl A, Raedsch R, Rudolph

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G. Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acids. Gastroenterology 1990;98:424-428. Stiehl A, Raedsch R, Rudolph G, Czygan P, Walker S. Analysis of bile acid glucuronides in urine: group separation on a lipophilic anion exchanger. Clin Chim Acta 1982;123:275-285. Alme B, Bremmelgaard A, Sjijvall J, Thomassen P. Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas liquid chromatography mass spectrometry. J Lipid Res 1977;18:339-361. Wilcoxon F, Wilcox RA. Some rapid approximate statistical procedures. Pearl River, NY: Lederle Laboratories, 1964. Sachs L. Angewandte Statistik. Statistische Methoden und ihre Anwendungen. New York: Springer-Verlag, 1978:426429. Eklund A, Norlander A, Norman A. Bile acid synthesis and expretion following release of total extrahepatic cholestasis by percutaneous transhepatic drainage. Eur J Clin Invest 1980;10:349-355. Nilsell K, Angelin B, Leijd B, and Einarsson K. Comparative effects of ursodeoxycholic acid and chenodeoxycholic acid on bile acid kinetics and biliary lipid secretion in humans. Evidence for different modes of action on bile acid synthesis. Gastroenterology 1983;85:1248-1256. Hardison WGM, Grundy SM. Effect of ursodeoxycholate and its taurine conjugate on bile acid synthesis and cholesterol absorption. Gastroenterology 1984;87:130-135.

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RF, Hofmann AF, Thistle JL, Schoenfield LJ. Effect of oral chenodeoxycholic acid on bile acid kinetics and biliary lipid composition in women with cholelithiasis. J Clin Invest 1973;52:2809-2821. Dupas JL, Hofmann AF. Passive jejunal absorption of bile acids in vivo: structure-activity relationships and rate limiting steps (abstr). Gastroenterology 1984;86:A1067. Igimi H, Carey MC. pH-solubility relations of chenodeoxycholit and ursodeoxycholic acids: physical-chemical basis for dissimilar solution and membrane phenomena. J Lipid Res 1980;21:72-90. Tint GS, Salen G, Shefer S. Effect of ursodeoxycholic acid and chenodeoxycholic acid on cholesterol and bile acid metabolism. Gastroenterology 1986;91:1007-1018. Stiehl A, Raedsch R, Rudolph G, Walker S. Effect of ursodeoxycholic acid on biliary bile acid and bile lipid composition in gallstone patients. Hepatology 1984;4:107-111. Stiehl A, Raedsch R, Czygan P, Glitz R, Manner Ch, Walker S, Kommerell B. Effects of biliary bile acid composition on biliary cholesterol saturation in gallstone patients treated with chenodeoxycholic acid and/or ursodeoxycholic acid. Gastroenterology 1980;79:1192-1198. Marteau P, Chazouilleres 0, Myara A, Jian R, Rambaud JC, Poupon R. Effect of chronic administration of ursodeoxycholit acid on the ileal absorption of endogenous bile acids in man. Hepatology 1990;12:1206-1208. Lillienau J, Munoz J, Longmire-Cook SJ, Crombie DL, Hofmann AF. Negative feedback regulation of the ileal bile acid transport system: the second site of regulation of the enterohepatic circulation. In: Paumgartner G, Stiehl A, Gerok W, eds. Bile acids as therapeutic agents from basic science to clinical practice. Dordrecht: Kluwer, 1991:163-165. Fedorowski T, Salen G, Colallilo A, Tint GS, Mosbach EH,

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Hall JC. Metabolism of ursodeoxycholic acid in man. Gastroenterology 1977;73:1131-1137. 31.Fromm H, Carlson GL, Hofmann AF, Farivar S, Amin P. Metabolism in man of 7-ketolithocholic acid: precursor of chenoand ursodeoxycholic acids. Am J Physiol 1980;239:G161G166. 32.Salen G, Tint GS, Verga D, Shefer S. The metabolism of 7-ketolithocholic acid in man. In: Paumgartner G, Stiehl A, Gerok W, eds. Bile acids and lipids. Lancaster, England: MTP Press, 1981:97-101. 33.Walker S, Stiehl A, Raedsch R, Kloters P, Kommerell B. Absorption of 7-ketolithocholic acid in rat jejunum, ileum and colon. Z Gastroenterol 1985;23:681-683. 34. Dumont M, Erlinger S, Uchman S. Hypercholeresis induced

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by ursodeoxycholic acid and 7-ketolithocholic acid in the rat: possible role of bicarbonate transport. Gastroenterology 1980;79:82-89. 35. Hofmann AF. Current concepts of biliary secretion. Dig Dis Sci 1989;34:16S-20s. 36. Northfield TC, Maudgal DP, Kupfer RM, Lanzini A. Gallstone dissolution and recurrence. In: Paumgartner G, Stiehl A, Gerok W, eds. Bile acids and cholesterol in health and disease. Boston: MTP Press, 1983:371-379. Received June 5, 1990. Accepted August 9, 1991. Address requests for reprints to: Siegfried Walker, M.D., Department of Gastroenterology, Robert-Bosch-Krankenhaus, Auerbachstrasse 110,W-7000 Stuttgart 50, Germany.

Intestinal absorption of ursodeoxycholic acid in patients with extrahepatic biliary obstruction and bile drainage.

Ursodeoxycholic acid (UDCA) dissolves cholesterol gallstones and improves liver function test results in patients with cholestatic liver diseases. Its...
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