Systemic availability and pharmacokinetics of nebulised budesonide in preschool children

doi:10.1136/adc.80.3.241

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Systemic availability and pharmacokinetics of nebulised budesonide in preschool children

L Agertoft,^a A Andersen,^a E Weibull,^b S Pedersen^a

^a Department of Paediatrics, Kolding Hospital, DK-6000 Kolding, Denmark, ^b Astra Draco AB, PO Box 34, S-221 00, Lund, Sweden

Correspondence to: Dr Agercroft.

Accepted 29 June 1998

AIM $---$ To evaluate the systemic availability and basic pharmacokinetic parameters of budesonide after nebulisation and intravenousadministration in preschool children with chronicasthma.
METHODS $---$ Plasma concentrations of budesonide were measured for three hours after an intravenous infusion of 125 µg budesonide. Thechildren then inhaled a nominal dose of 1 mg budesonide throughthe mouthpiece of a Pari LC Jet Plus nebuliser connected to aPari Master compressor, and the plasma concentrations of budesonidewere measured for another six hours. The amount of budesonideinhaled by the patient ("dose to subject") was determined by subtractingfrom the amount of budesonide put into the nebuliser, the amountremaining in the nebuliser after nebulisation, the amount emittedto the ambient air (filter), and the amount found in the mouthrinsingwater.
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 wasestimated 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 to0.62), steady state volume of distribution 55 litres (95% CI,45 to 68), and the terminal half life was 2.3 hours (95% CI, 2.0to 2.6).
CONCLUSIONS $---$ Approximately 6% of the nominal dose (26% of the dose to subject) reached the systemic circulation of young children afterinhalation of nebulised budesonide. This is about half the systemicavailability found in healthy adults using the samenebuliser.

Key messages

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

Keywords: pharmacokinetics; nebulised treatment; corticosteroids; systemic availability

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