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. Aim: 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. AUC0-∞ 7.7 ± 5.1 h ng/mL, Cmax 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. © 2006 Blackwell Publishing Ltd.