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. 1999 Mar;80(3):241–247. doi: 10.1136/adc.80.3.241

Systemic availability and pharmacokinetics of nebulised budesonide in preschool children

L Agertoft 1, A Andersen 1, E Weibull 1, S Pedersen 1
PMCID: PMC1717853  PMID: 10325704

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, 2.0to 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.



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Selected References

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  1. Agertoft L., Pedersen S. Importance of the inhalation device on the effect of budesonide. Arch Dis Child. 1993 Jul;69(1):130–133. doi: 10.1136/adc.69.1.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agertoft L., Pedersen S. Influence of spacer device on drug delivery to young children with asthma. Arch Dis Child. 1994 Sep;71(3):217–220. doi: 10.1136/adc.71.3.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bisgaard H., Pedersen S., Nikander K. Use of budesonide Turbuhaler in young children suspected of asthma. Eur Respir J. 1994 Apr;7(4):740–742. doi: 10.1183/09031936.94.07040740. [DOI] [PubMed] [Google Scholar]
  4. Bredberg U., Karlsson M. O., Borgström L. A comparison between the semisimultaneous and the stable isotope techniques for bioavailability estimation of terbutaline in humans. Clin Pharmacol Ther. 1992 Sep;52(3):239–248. doi: 10.1038/clpt.1992.136. [DOI] [PubMed] [Google Scholar]
  5. Chua H. L., Collis G. G., Newbury A. M., Chan K., Bower G. D., Sly P. D., Le Souef P. N. The influence of age on aerosol deposition in children with cystic fibrosis. Eur Respir J. 1994 Dec;7(12):2185–2191. doi: 10.1183/09031936.94.07122185. [DOI] [PubMed] [Google Scholar]
  6. Devadason S. G., Everard M. L., MacEarlan C., Roller C., Summers Q. A., Swift P., Borgstrom L., Le Souëf P. N. Lung deposition from the Turbuhaler in children with cystic fibrosis. Eur Respir J. 1997 Sep;10(9):2023–2028. doi: 10.1183/09031936.97.10092023. [DOI] [PubMed] [Google Scholar]
  7. Everard M. L., Clark A. R., Milner A. D. Drug delivery from holding chambers with attached facemask. Arch Dis Child. 1992 May;67(5):580–585. doi: 10.1136/adc.67.5.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Everard M. L., Hardy J. G., Milner A. D. Comparison of nebulised aerosol deposition in the lungs of healthy adults following oral and nasal inhalation. Thorax. 1993 Oct;48(10):1045–1046. doi: 10.1136/thx.48.10.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holford N. H. A size standard for pharmacokinetics. Clin Pharmacokinet. 1996 May;30(5):329–332. doi: 10.2165/00003088-199630050-00001. [DOI] [PubMed] [Google Scholar]
  10. Ilangovan P., Pedersen S., Godfrey S., Nikander K., Noviski N., Warner J. O. Treatment of severe steroid dependent preschool asthma with nebulised budesonide suspension. Arch Dis Child. 1993 Mar;68(3):356–359. doi: 10.1136/adc.68.3.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Karlsson M. O., Bredberg U. Estimation of bioavailability on a single occasion after semisimultaneous drug administration. Pharm Res. 1989 Sep;6(9):817–821. doi: 10.1023/a:1015939917646. [DOI] [PubMed] [Google Scholar]
  12. Lødrup Carlsen K. C., Nikander K., Carlsen K. H. How much nebulised budesonide reaches infants and toddlers? Arch Dis Child. 1992 Sep;67(9):1077–1079. doi: 10.1136/adc.67.9.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mallol J., Rattray S., Walker G., Cook D., Robertson C. F. Aerosol deposition in infants with cystic fibrosis. Pediatr Pulmonol. 1996 May;21(5):276–281. doi: 10.1002/(SICI)1099-0496(199605)21:5<276::AID-PPUL2>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  14. Pedersen S., Steffensen G., Ekman I., Tönnesson M., Borgå O. Pharmacokinetics of budesonide in children with asthma. Eur J Clin Pharmacol. 1987;31(5):579–582. doi: 10.1007/BF00606634. [DOI] [PubMed] [Google Scholar]
  15. Smaldone G. C. Deposition patterns of nebulized drugs: is the pattern important? J Aerosol Med. 1994;7(Suppl 1):S25–S32. doi: 10.1089/jam.1994.7.suppl_1.s-25. [DOI] [PubMed] [Google Scholar]
  16. Smaldone G. C., Fuhrer J., Steigbigel R. T., McPeck M. Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection. Am Rev Respir Dis. 1991 Apr;143(4 Pt 1):727–737. doi: 10.1164/ajrccm/143.4_Pt_1.727. [DOI] [PubMed] [Google Scholar]
  17. Thorsson L., Edsbäcker S., Conradson T. B. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J. 1994 Oct;7(10):1839–1844. doi: 10.1183/09031936.94.07101839. [DOI] [PubMed] [Google Scholar]
  18. Vikre-Jørgensen J., Agertoft L., Pedersen S. Dose titration of nebulized budesonide in young children. Pediatr Pulmonol. 1997 Apr;23(4):270–277. doi: 10.1002/(sici)1099-0496(199704)23:4<270::aid-ppul4>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  19. Vonesh E. F., Carter R. L. Mixed-effects nonlinear regression for unbalanced repeated measures. Biometrics. 1992 Mar;48(1):1–17. [PubMed] [Google Scholar]
  20. Wennergren G., Nordvall S. L., Hedlin G., Möller C., Wille S., Asbrink Nilsson E. Nebulized budesonide for the treatment of moderate to severe asthma in infants and toddlers. Acta Paediatr. 1996 Feb;85(2):183–189. doi: 10.1111/j.1651-2227.1996.tb13989.x. [DOI] [PubMed] [Google Scholar]
  21. Wildhaber J. H., Devadason S. G., Hayden M. J., Eber E., Summers Q. A., LeSouëf P. N. Aerosol delivery to wheezy infants: a comparison between a nebulizer and two small volume spacers. Pediatr Pulmonol. 1997 Mar;23(3):212–216. doi: 10.1002/(sici)1099-0496(199703)23:3<212::aid-ppul7>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]

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