Systemic availability and pharmacokinetics of nebulised budesonide in preschool children

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Abstract
AIM To evaluate the systemic availability and basic pharmacokinetic parameters of budesonide after nebulisation and intravenous administration in preschool children with chronic asthma. METHODS Plasma concentrations of budesonide were measured for three hours after an intravenous infusion of 125 μg budesonide. The children then inhaled a nominal dose of 1 mg budesonide through the mouthpiece of a Pari LC Jet Plus nebuliser connected to a Pari Master compressor, and the plasma concentrations 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 amount 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 the 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 nominal dose (95% confidence intervals (CI), 4.6% to 8.1%) or 26.3% of the dose 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 subject) reached the systemic circulation of young children after inhalation of nebulised budesonide. This is about half the systemic availability found in healthy adults using the same nebuliser. Approximately 6% of the nominal dose of budesonide (26% of dose to subject) reaches the systemic circulation of young children after inhalation from a Pari LC Jet Plus nebuliser Deposition of drug in the intrapulmonary airways seems to be much lower in young children than in adults using the same nebuliser Budesonide clearance/kg body weight is higher in young children than in adults The low systemic availability in combination with a higher clearance/kg body weight in young children means that these age groups can use the same nebulised budesonide dose as adults without an increased risk of unwanted systemic effects. Therefore, dosing of nebulised budesonide in mg/kg body weight to reduce the risk of unwanted systemic effects is not warranted A filter inhalation accurately assesses the inhaled dose of budesonide in children using a nebuliser. However, in the individual patient it is only a crude surrogate marker of the systemic availability and dose of budesonide deposited in the intrapulmonary airways