title: Side effects of budesonide in liver cirrhosis due to chronic autoimmune hepatitis: influence of hepatic metabolism versus portosystemic shunts on a patient complicated with HCC.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine III, University of Technology Aachen, Aachen, Germany. ageier@ukaachen.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Geier
authors.forename: Carsten
authors.initials: C
authors.lastname: Gartung
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Dietrich
authors.forename: Hermann E
authors.initials: HE
authors.lastname: Wasmuth
authors.forename: Patrick
authors.initials: P
authors.lastname: Reinartz
authors.forename: Siegfried
authors.initials: S
authors.lastname: Matern
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019819:Budesonide / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000150:complications*; D005260:Female; D019693:Hepatitis, Autoimmune / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000150:complications*; D011170:Portasystemic Shunt, Surgical
chemical_list: D000893:Anti-Inflammatory Agents; D019819:Budesonide