In 4-6 years old asthmatic children, the systemic availability of budesonide following administration of Budesonide Nebuliser Suspension via a jet nebuliser (Pari LC Jet Plus® with Pari Master® compressor) is approximately 6% of the nominal dose and 26% of the dose delivered to the patients. The systemic availability in children is about half of that in healthy adults. The maximal plasma concentration, occurring approximately 20 min after start of nebulisation is approximately nmol/L in 4-6 years old asthmatic children after a 1 mg dose. The exposure (Cmax and AUC) of budesonide following administration of a single 1 mg dose by nebulisation to 4-6 year old children is comparable to that in healthy adults given the same delivered dose by the same nebuliser system.
In an integrated study with separate induction and maintenance trials, Sanborn et al (2013) evaluated intravenous VDZ therapy (300 mg) in adults with active CD. In the induction trial, 368 patients were randomly assigned to receive VDZ or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label VDZ at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to VDZ were randomly assigned to receive placebo or VDZ every 8 or 4 weeks until week 52. At week 6, a total of % of the patients in cohort 1 who received VDZ and % who received placebo were in clinical remission (., had a score on the CDAI of less than or equal to 150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (p = ); a total of % and % of the patients, respectively, had a CDAI-100 response (greater than or equal to 100-point decrease in the CDAI score) (p = ). Among patients in cohorts 1 and 2 who had a response to induction therapy, % and % of those assigned to VDZ every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with % assigned to placebo (p < and p = for the 2 VDZ groups, respectively, versus placebo). Antibodies against VDZ developed in % of the patients. Naso-pharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving VDZ than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events ( % versus %), infections ( % versus %), and serious infections ( % versus %). The authors concluded that VDZ-treated patients with active CD were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive VDZ (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with VDZ.