AIM: To investigate the systemic availability of budesonide in a patient with Child A cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma, who developed serious side effects. METHODS: Serum levels of budesonide, 6beta-OH-budesonide and 16alpha-OH-prednisolone were measured by HPLC/MS/MS; portosystemic shunt-index (SI) was determined by 99mTc nuclear imaging. All values were compared with a matched control patient without side effects. RESULTS: Serum levels of budesonide were 13-fold increased in the index patient. The ratio between serum levels of the metabolites 6beta-OH-budesonide and 16alpha-OH-prednisolone, respectively, and serum levels of budesonide was diminished (1.0 vs. 4.0 for 6beta-OH-budesonide, 4.2 vs. 10.7 for 16alpha-OH-prednisolone). Both patients had portosystemic SI (5.7% and 3.1%) within the range of healthy subjects. CONCLUSION: Serum levels of budesonide vary up to 13-fold in AIH patients with Child A cirrhosis in the absence of relevant portosystemic shunting. Reduced hepatic metabolism, as indicated by reduced metabolite-to-drug ratio, rather than portosystemic shunting may explain systemic side effects of this drug in cirrhosis.
AIM: To investigate the systemic availability of budesonide in a patient with ChildA cirrhosis due to autoimmune hepatitis (AIH) and primary hepatocellular carcinoma, who developed serious side effects. METHODS: Serum levels of budesonide, 6beta-OH-budesonide and 16alpha-OH-prednisolone were measured by HPLC/MS/MS; portosystemic shunt-index (SI) was determined by 99mTc nuclear imaging. All values were compared with a matched control patient without side effects. RESULTS: Serum levels of budesonide were 13-fold increased in the index patient. The ratio between serum levels of the metabolites 6beta-OH-budesonide and 16alpha-OH-prednisolone, respectively, and serum levels of budesonide was diminished (1.0 vs. 4.0 for 6beta-OH-budesonide, 4.2 vs. 10.7 for 16alpha-OH-prednisolone). Both patients had portosystemic SI (5.7% and 3.1%) within the range of healthy subjects. CONCLUSION: Serum levels of budesonide vary up to 13-fold in AIH patients with ChildA cirrhosis in the absence of relevant portosystemic shunting. Reduced hepatic metabolism, as indicated by reduced metabolite-to-drug ratio, rather than portosystemic shunting may explain systemic side effects of this drug in cirrhosis.
Authors: M Leuschner; K P Maier; J Schlichting; S Strahl; G Herrmann; H H Dahm; H Ackermann; J Happ; U Leuschner Journal: Gastroenterology Date: 1999-10 Impact factor: 22.682
Authors: F Alvarez; P A Berg; F B Bianchi; L Bianchi; A K Burroughs; E L Cancado; R W Chapman; W G Cooksley; A J Czaja; V J Desmet; P T Donaldson; A L Eddleston; L Fainboim; J Heathcote; J C Homberg; J H Hoofnagle; S Kakumu; E L Krawitt; I R Mackay; R N MacSween; W C Maddrey; M P Manns; I G McFarlane; K H Meyer zum Büschenfelde; M Zeniya Journal: J Hepatol Date: 1999-11 Impact factor: 25.083
Authors: S Shiomi; T Kuroki; T Ueda; T Takeda; N Ikeoka; S Nishiguchi; S Nakajima; K Kobayashi; H Ochi Journal: Am J Gastroenterol Date: 1995-03 Impact factor: 10.864
Authors: J Y Wang; S L Chen; F Z Chen; W G Xu; D C Hu; X F Chen; G Jin; H Y Liu Journal: J Gastroenterol Hepatol Date: 1995 Mar-Apr Impact factor: 4.029