Pharmacokinetics of budesonide controlled ileal release capsules in children and adults with active Crohn's disease (original) (raw)
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Pharmacokinetics and pharmacodynamic action of budesonide in children with Crohn's disease
Alimentary Pharmacology and Therapeutics, 2006
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. AUC 0)¥ 7.7 AE 5.1 h ng/mL, C max 1.8 AE 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.
Journal of Crohn's and Colitis, 2013
Background and aims: Current treatments for Japanese patients with active Crohn's disease have not proved optimal, and new treatment options are required. The present study therefore evaluated the efficacy and tolerability of oral budesonide in Japanese patients with mild-tomoderate active Crohn's disease. Methods: In this multicentre, double-blind, randomized, parallel-group, Phase II study, patients (18-65 years) with baseline Crohn's Disease Activity Index (CDAI) score ≥ 200 were randomized to once-daily (od) oral budesonide 9 mg or 15 mg, or matching placebo, for 8 weeks. Concomitant therapy with sulfasalazine or 5-aminosalicylic acid, and nutritional therapy, was allowed. The rate of remission (defined as CDAI score ≤ 150) after 8 weeks' treatment (primary variable), health-related quality of life (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ]), and tolerability were assessed. Results: 77 patients were randomized and 63 completed the study. The proportion of budesonidetreated patients with remission after 8 weeks' treatment was higher compared with placebo (23.1%, 28.0%, and 11.5% for budesonide 9 mg, 15 mg, and placebo, respectively; no significant difference). The mean change from baseline to week 8 in CDAI total score (−48.0, −58.2, and A v a i l a b l e o n l i n e a t w w w . s c i e n c e d i r e c t . c o m Journal of Crohn's and Colitis (2013) 7, 239-247 −27.2, respectively) and IBDQ total score (10.8, 23.2, and 6.5, respectively) was greater for budesonide-treated patients than placebo recipients. While budesonide 9 mg and 15 mg demonstrated similar efficacy, budesonide 9 mg caused fewer drug-and glucocorticosteroidrelated adverse events and less adrenal suppression. Conclusions: Oral budesonide 9 mg od (for up to 8 weeks) may offer a new treatment option for Japanese patients with mild-to-moderate active Crohn's disease.
Budesonide as maintenance treatment in Crohn's disease: a placebo‐controlled trial
Aim: To assess the efficacy and safety of budesonide capsules 6 mg daily for prolongation of time to relapse and maintenance of remission in patients with Crohn's disease (CD) affecting the ileum and/or ascending colon. Methods: In a double-blind, placebo-controlled, multicentre trial, 110 patients with CD, who had previously achieved remission in a placebo-controlled trial of budesonide 9 mg daily, were randomly assigned to receive budesonide 6 mg once daily or placebo for 52 weeks. Primary outcome measure was time to relapse [CD activity index (CDAI) of >150 plus an increase of at least 60 points from study entry or withdrawal due to clinical deterioration]. Results: Median time to relapse was 360 days for budesonide patients; 169 days for placebo patients (P ¼ 0.132). No significant differences were seen between groups in relapse rates at 1 year. Budesonide was safe and well tolerated, with a similar adverse events profile to placebo. Conclusion: Patients treated with budesonide 6 mg once daily had a trend towards a prolonged time to relapse and lower CDAI scores compared with patients treated with placebo, but relapse rates were not significantly different at the 1-year end point.
Oral budesonide for maintenance of remission of Crohn’s disease: a pooled safety analysis
Alimentary Pharmacology & Therapeutics, 2009
Budesonide exhibits similar efficacy to systemic glucocorticosteroids (GCSs) in Crohn's disease (CD), but with fewer adverse events (AEs). Aim To evaluate budesonide's safety profile in CD patients, in particular, incidences of clinically important AEs known to be associated with systemic GCSs. Five 1-year, double-blind, placebo-controlled trials evaluating budesonide for mild-to-moderate CD were pooled for analysis. The highest incidence rates of AEs were gastrointestinal- and endocrine systems-related in both groups (budesonide 6 mg/day, n = 208; placebo, n = 209). Incidence rates were similar, except for higher incidence of endocrine disorders in budesonide versus placebo patients (P = 0.0042) caused by a higher overall occurrence of cutaneous GCS symptoms (P = 0.0036) in the budesonide group; differences in individual symptoms were nonsignificant. Percentage of patients with normal adrenal function was significantly lower at 13 weeks (three of five studies), but not at 52 weeks (two studies) in the budesonide versus placebo groups. Occurrence of clinically important or serious AEs associated with systemic GCSs, including sepsis, cataracts, adrenal insufficiency was rare and similar between groups. Budesonide treatment for up to 1 year is well-tolerated in CD patients, with an AE profile similar to placebo and only rare occurrences of clinically important AEs associated with systemic GCSs.