8 research outputs found
Der Effekt von Ursodeoxycholsäure auf den Cytochrom P450 3A-Metabolismus bei primär biliärer Zirrhose und gesunden Probanden
Ursodeoxycholsäure ist kein klinisch relevanter Induktor der CYP3A-abhängigen Biotransformatio
No relevant effect of ursodeoxycholic acid on cytochrome P450 3A metabolism in primary biliary cirrhosis
Induction of cytochrome P450 3A (CYP3A) has been suggested as a mechanism of action of ursodeoxycholic acid (UDCA) in cholestasis. CYP3A is of key importance in human drug metabolism, being involved in presystemic extraction of more than 50% of all drugs currently available and of various endogenous compounds. Therefore, we compared the induction potential of UDCA with that of the prototypical inducer rifampicin in a human model study with the CYP3A substrates budesonide and cortisol. Twelve patients with early-stage primary biliary cirrhosis and eight healthy volunteers were treated with UDCA (15 mg/kg daily) for 3 weeks and subsequently with rifampicin (600 mg/d) for 1 week. Extensive pharmacokinetic profiling of oral budesonide (3 mg) was performed by determination of budesonide and phase I metabolites (6beta-hydroxybudesonide, 16alpha-hydroxyprednisolone) in plasma and urine at baseline and at the end of each treatment. In parallel, urinary 6beta-hydroxycortisol, a validated marker of CYP3A induction, was determined. UDCA did not affect biotransformation of budesonide and urinary excretion of 6beta-hydroxycortisol either in patients or in healthy volunteers. Ratios of areas under plasma concentration-time curves (AUC(0-12 h) during UDCA/AUC(0-12 h) before UDCA) of both metabolites were not higher than those of budesonide itself. In contrast, administration of rifampicin markedly induced CYP3A metabolism, resulting in abolished budesonide plasma levels and high urinary excretion of 6beta-hydroxycortisol. Metabolite formation was enhanced by rifampicin, but not by UDCA (e.g., AUC(16alpha-hydroxyprednisolone)/AUC(budesonide) in patients: baseline, 8.6 +/- 3.9; UDCA, 10.7 +/- 7.1; rifampicin, 527.0 +/- 248.7). In conclusion, UDCA is not a relevant inducer of CYP3A enzymes in human
Definition and prognostic relevance of the salve grading and staging system for alcohol-related liver disease
Development and prognostic relevance of a histologic grading and staging system for alcohol-related liver disease
The SALVE Histopathology Group (SHG) developed and validated a grading and staging system for the clinical and full histological spectrum of alcohol-related liver disease (ALD) and evaluated its prognostic utility in a multinational cohort of 445 patients