Pharmacokinetics and pharmacodynamic action of budesonide in children with Crohn's disease.
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.
Dilger
K
K
Dr Falk Pharma GmbH, Freiburg, Germany.
Alberer
M
M
Busch
A
A
Enninger
A
A
Behrens
R
R
Koletzko
S
S
Stern
M
M
Beckmann
C
C
Gleiter
C H
CH
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
D000893:Anti-Inflammatory Agents; D019819:Budesonide; D006854:Hydrocortisone