Systemic availability and pharmacokinetics of nebulised budesonide in preschool children

Aim-To evaluate the systemic availability and basic pharmacokinetic paramet ers of budesonide after nebulisation and intravenous administration in pres chool children with chronic asthma. Methods-Plasma concentrations of budesonide were measured for three hours a fter an intravenous infusion of 125 mu g budesonide. The children then inha led a nominal dose of 1 mg budesonide through the mouthpiece of a Pari Le: Jet Plus nebuliser connected to a Pari Master compressor, and the plasma co ncentrations of budesonide were measured for another six hours. The amount of budesonide inhaled by the patient ("dose to subject") was determined by subtracting from the amount of budesonide put into the nebuliser, the amoun t remaining in the nebuliser after nebulisation, the amount emitted to the ambient air (filter), and the amount found in the mouth rinsing water. Results-Ten patients aged 3 to 6 years completed both the intravenous and t he inhaled treatment. The mean dose to subject was 23% of the nominal dose. The systemic availability of budesonide was estimated to be 6.1% of the no minal dose (95% confidence intervals (CI), 4.6% to 8.1%) or 26.3% of the do se to subject (95% CI, 20.3% to 34.1%). Budesonide clearance was 0.54 l/min (95% CI, 0.46 to 0.62), steady state volume of distribution 55 litres (95% CI, 45 to 68), and the terminal half life was 2.3 hours (95% CI, 2.0 to 2. 6). Conclusions-Approximately 6% of the nominal dose (26% of the dose to subjec t) reached the systemic circulation of young children after inhalation of n ebulised budesonide. This is about half the systemic availability found in healthy adults using the same nebuliser.