title: Pharmacokinetics and pharmacodynamic action of budesonide in children with Crohn's disease.
abstract: BACKGROUND
  Budesonide is effective as initial therapy of mild to moderate Crohn's disease in adults. Superior tolerability to conventional corticosteroids might be attributed to extensive first-pass metabolism of budesonide by cytochrome P450 3A.
  
  
  OBJECTIVE
  To evaluate biotransformation and pharmacodynamic action of budesonide in children.
  
  
  METHODS
  Drug disposition and effects on endogenous cortisol were evaluated in 12 children with Crohn's disease (5-15 years) after first intake of 3 mg budesonide (single dose), and again after 1 week of thrice daily dosing (steady-state). The parent drug and cytochrome P450 3A-dependent metabolites were analysed in blood and urine.
  
  
  RESULTS
  Pharmacokinetic parameters of budesonide following single-dose administration (e.g. AUC(0-infinity) 7.7+/-5.1 h ng/mL, C(max) 1.8+/-1.2 ng/mL) did not change upon multiple dosing. Overall systemic elimination of budesonide reflected by clearance and half-life was not different between children and adults. After 1 week of treatment reversible adrenal suppression was observed - most pronounced in children aged below 12 years.
  
  
  CONCLUSIONS
  Disposition of oral budesonide appears to be similar between children and adults, but the doctor has to be aware of an increased risk for adrenal suppression in paediatric patients.
authors.affiliation: Dr Falk Pharma GmbH, Freiburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Dilger
authors.forename: M
authors.initials: M
authors.lastname: Alberer
authors.forename: A
authors.initials: A
authors.lastname: Busch
authors.forename: A
authors.initials: A
authors.lastname: Enninger
authors.forename: R
authors.initials: R
authors.lastname: Behrens
authors.forename: S
authors.initials: S
authors.lastname: Koletzko
authors.forename: M
authors.initials: M
authors.lastname: Stern
authors.forename: C
authors.initials: C
authors.lastname: Beckmann
authors.forename: C H
authors.initials: CH
authors.lastname: Gleiter
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019819:Budesonide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male
chemical_list: D000893:Anti-Inflammatory Agents; D019819:Budesonide; D006854:Hydrocortisone