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Toxicity of ursodeoxycholic acid (UDCA) in chronic cholestasis assessed by quantititive liver function tests
RENAL RESISTANCE TO ATRIAL NATRIURETIC PEPTIDE (ANP) IN EXPERIMENTAL CIRRHOSIS WITH ASCITES DISAPPEARS AFTER NORMALIZATION OF ARTERIAL PRESSURE WITH NOREPINEPHRINE (NE). C.L6pez, W. Jim~nez, V.Arroyo, J.Gaya, J . C l S r i a , F.Rivera and J. Rod~s. L i v e r Unit and Hormonal L a b o r a t o r y . H o s p i t a l C l i n i c i P r o v i n c l a l . Barcelona. Spain. The n a t r i u r e t i c e f f e c t of ANP is markedly reduced in c i r r h o s i s w l t h a s c i t e s . It has been proposed t h a t t h i s a b n o r m a l i t y is due to the o v e r a c t l v l t y of endogenous a n t l n a t r i u r e t i c systems and/or t o a l t e r a t i o n s in ANP t u b u l a r r e c e p t o r s . This study i n v e s t l g a t e s i f the blunted n a t r i u r e t i c response to ANP is r e l a t e d to the a l t e r e d systemic hemodynamics present in c i r r h o s i s with ascltes. ANP (a bolus of 1 g f o l l o w e d by a constant i n f u s l o n o f 33 n g / m n ) was given iv to I0 c o n t r o l r a t s (Group I: mean a r t e r i a l pressure, MAP, 125±I mmHg), I0 r a t s w i t h carbon t e t r a c h l o r i d e induced c i r r h o s i s and a s c i t e s (Group 11; MAP, 103±2; p
103
104
TOXICITY OF URSODEOXYCHOLIC ACID (UDCA) ASSESSED BY QUANTITITIVE LIVER FUNCTION TESTS
IN
CHRONIC
CHOLESTASIS
E. Lotterer, F.E. Bauer and J. Bircher Division of Clinical Pharmacolgy, University of Goettingen, FRG
On the basis that UDCA is less detergent than endogenous bile acids Poupon et al. (Lancet 1987, Vol I:834) have proposed to treat patients with primary biliary cirrhosis (PBC) with UDCA. Toxicity of UDCA in patients with chronic cholestasis, however, is as yet unknown. Nine patients with PBC and two with primary sclerosing cholangitis (PSC) were therefore treated with UDCA 15 mg/kg/day. Diagnoses were based on typical clinical and laboratory findings and on compatible histology. The aminopyrine breath test (ABT), the galactose elimination capacity (GEC) and the extrarenal sorbitol clearance (S-C1) were measured before and after 6 months. The S-C1 was applied to assess liver plasma flow (Zeeh, et al., Gastroenterology, in press). Results: After one month of treatment biochemical changes similar to those of Poupon et al. were observed: median alkaline phosphatase fell from 511 to 294 U/I (p ( 0 , 0 1 ) , r-glutamyl transferase from 177 to 85 U/I (p (0,01) and GPT from 43 to 28 U/I (p < 0,05). Pruritus improved in all affected patients. Before UDCA the ABT was 0,66 (range 0,05 - 1,17) units, the GEC 369 (187 - 442) mg/min and the S-C1 624 (290 - 924) ml/min. Although not all patients have concluded the 6 month period, as of now no significant changes in quantitative liver function tests were found. Conclusions: These results confirm the beneficial effects of UDCA on pruritus and biochemical abnormalities. As yet there is no evidence for toxicity of UDCA as assessed by quantitative liver function tests. N.B.: By the end of July 1988 all patients will have completed the 6 month period of observation.
$54
103
104
TOXICITY OF URSODEOXYCHOLIC ACID (UDCA) ASSESSED BY QUANTITITIVE LIVER FUNCTION TESTS
IN
CHRONIC
CHOLESTASIS
E. Lotterer, F.E. Bauer and J. Bircher Division of Clinical Pharmacolgy, University of Goettingen, FRG
On the basis that UDCA is less detergent than endogenous bile acids Poupon et al. (Lancet 1987, Vol I:834) have proposed to treat patients with primary biliary cirrhosis (PBC) with UDCA. Toxicity of UDCA in patients with chronic cholestasis, however, is as yet unknown. Nine patients with PBC and two with primary sclerosing cholangitis (PSC) were therefore treated with UDCA 15 mg/kg/day. Diagnoses were based on typical clinical and laboratory findings and on compatible histology. The aminopyrine breath test (ABT), the galactose elimination capacity (GEC) and the extrarenal sorbitol clearance (S-C1) were measured before and after 6 months. The S-C1 was applied to assess liver plasma flow (Zeeh, et al., Gastroenterology, in press). Results: After one month of treatment biochemical changes similar to those of Poupon et al. were observed: median alkaline phosphatase fell from 511 to 294 U/I (p ( 0 , 0 1 ) , r-glutamyl transferase from 177 to 85 U/I (p (0,01) and GPT from 43 to 28 U/I (p < 0,05). Pruritus improved in all affected patients. Before UDCA the ABT was 0,66 (range 0,05 - 1,17) units, the GEC 369 (187 - 442) mg/min and the S-C1 624 (290 - 924) ml/min. Although not all patients have concluded the 6 month period, as of now no significant changes in quantitative liver function tests were found. Conclusions: These results confirm the beneficial effects of UDCA on pruritus and biochemical abnormalities. As yet there is no evidence for toxicity of UDCA as assessed by quantitative liver function tests. N.B.: By the end of July 1988 all patients will have completed the 6 month period of observation.
$54