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. 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-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.

[Real-time PCR assay for rapid detection of clarithromycin-resistant helicobacter pylori in gastric biopsy specimens]. / Schneller Nachweis von clarithromycinresistenten Helicobacter pylori in der Magenbiopsie mittels Real-Time-PCR.

The main cause for failure of Helicobacter pylori eradication therapy is resistance to clarithromycin which is due to point mutations. The use of real-time PCR allows the detection of these mutations directly on biopsy specimens within a few hours. In our routine laboratory, we compared LightCycler PCR to conventional detection and susceptibility testing of H. pylori by culture. PCR showed a positive result for H. pylori in 74 specimens. PCR was confirmed by culture in 69 specimens. In five specimens which were positive by PCR but negative on culture the (13)C urea breath test confirmed the PCR results. Sensitivity and specificity of our LightCycler assay for the detection of H. pylori in biopsy specimens were both 100 %. In 26 out of 68 specimens conventional susceptibility testing yielded resistance to clarithromycin. Corresponding point mutations were found in 24 of these specimens. Compared to culture, PCR gave a false-resistant, respectively, a false sensitive result in one specimen each. In another specimen, culture yielded a resistant strain whereas PCR detected both a resistant mutant and the wild-type strain. From two other specimens clarithromycin-sensitive strains were cultured but both a wild-type strain and a mutant were detected by PCR. Sensitivity and specificity of LightCycler PCR for resistance to clarithromycin were 96.2 % and 97.6 %, respectively. This assay had an accuracy comparable to culture and could be performed within 3 hours, allowing it to be used before the administration of H. pylori eradication therapy.