Abstract
1. The aim of this pharmacokinetic study was to evaluate to what extent oropharyngeal deposition of drug contributes to the systemic availability of budesonide inhaled from a dry powder inhaler (Turbuhaler). 2. The design was a randomized cross-over study in eight children aged 7-13 years. The plasma concentrations of the two epimers of budesonide (22R and 22S) after inhalation of 1 mg budesonide from a Turbuhaler were compared with the plasma concentrations obtained when the absorption of the drug deposited in the oropharynx was blocked by drinking and rinsing the mouth with charcoal before and after the inhalation. 3. The plasma concentrations of budesonide were significantly reduced by the charcoal treatment (P < 0.01) and the area under the time vs plasma concentration curve 0-4 h was significantly reduced from 9.5 to 8.0 mmol l-1 h for 22S (P < 0.01) and from 7.6 to 5.7 mmol l-1 h for 22R (P < 0.01). 4. The plasma concentrations and the AUCs after both Turbuhaler administrations were markedly higher than those obtained in earlier studies using other inhalers suggesting a higher intrapulmonary deposition of drug after Turbuhaler treatment. 5. It is concluded that oropharyngeal deposition of drug accounts for about 20% of the total systemic availability of budesonide inhaled from Turbuhaler. Thus, the main contribution to the system comes from budesonide absorbed in the airways.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Chanoine F., Grenot C., Heidmann P., Junien J. L. Pharmacokinetics of butixocort 21-propionate, budesonide, and beclomethasone dipropionate in the rat after intratracheal, intravenous, and oral treatments. Drug Metab Dispos. 1991 Mar-Apr;19(2):546–553. [PubMed] [Google Scholar]
- Dolovich M., Ruffin R. E., Roberts R., Newhouse M. T. Optimal delivery of aerosols from metered dose inhalers. Chest. 1981 Dec;80(6 Suppl):911–915. [PubMed] [Google Scholar]
- Engel T., Heinig J. H., Malling H. J., Scharling B., Nikander K., Madsen F. Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler. Allergy. 1989 Apr;44(3):220–225. doi: 10.1111/j.1398-9995.1989.tb02266.x. [DOI] [PubMed] [Google Scholar]
- Hamilton R. A., Garnett W. R., Kline B. J. Determination of mean valproic acid serum level by assay of a single pooled sample. Clin Pharmacol Ther. 1981 Mar;29(3):408–413. doi: 10.1038/clpt.1981.56. [DOI] [PubMed] [Google Scholar]
- Johansson S. A., Andersson K. E., Brattsand R., Gruvstad E., Hedner P. Topical and systemic glucocorticoid potencies of budesonide and beclomethasone dipropionate in man. Eur J Clin Pharmacol. 1982;22(6):523–529. doi: 10.1007/BF00609625. [DOI] [PubMed] [Google Scholar]
- Martin L. E., Tanner R. J., Clark T. J., Cochrane G. M. Absorption and metabolism of orally administered beclomethsone dipropionate. Clin Pharmacol Ther. 1974 Mar;15(3):267–275. doi: 10.1002/cpt1974153267. [DOI] [PubMed] [Google Scholar]
- Newman S. P., Morén F., Pavia D., Little F., Clarke S. W. Deposition of pressurized suspension aerosols inhaled through extension devices. Am Rev Respir Dis. 1981 Sep;124(3):317–320. doi: 10.1164/arrd.1981.124.3.317. [DOI] [PubMed] [Google Scholar]
- Newman S. P., Pavia D., Morén F., Sheahan N. F., Clarke S. W. Deposition of pressurised aerosols in the human respiratory tract. Thorax. 1981 Jan;36(1):52–55. doi: 10.1136/thx.36.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Ryrfeldt A., Andersson P., Edsbäcker S., Tönnesson M., Davies D., Pauwels R. Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis Suppl. 1982;122:86–95. [PubMed] [Google Scholar]
- Selroos O., Halme M. Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler. Thorax. 1991 Dec;46(12):891–894. doi: 10.1136/thx.46.12.891. [DOI] [PMC free article] [PubMed] [Google Scholar]