The influence of orally deposited budesonide on the systemic availability of budesonide after inhalation from a Turbuhaler.

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 1-1 h for 22S (P < 0.01) and from 7.6 to 5.7 mmol 1-1 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.

Pharmacokinetics of inhaled drugs

“…The should result in greater steady-state accumulation during repeated dosing. This is supported by a study where absorption of the same dose of budesonide was higher comparing turbuhaler with nebuhaler ( both without there was a large step-up in adrenal suppression between single and repeated doses of fluticasone 1000 mg twice charcoal ) being two-fold greater [ 25]. Allowing for greater oropharangeal deposition of budesonide with a daily (25% vs 55% suppression), whereas with budesonide 800 mg twice daily this effect was much less turbuhaler than with a nebuhaler, these data suggest an almost two-fold greater lung delivery of budesonide pronounced (26% vs 34% suppression) [32 ].…”

Airway deposition and airway effects of antiasthma drugs delivered from metered-dose inhalers

“…The only significant difference was an increased need for β 2 -agonist as rescue medication in the pMDI plus Nebuhaler® group. The effect data must be compared to plasma concentrations of the drug after inhalation from a pMDI plus Nebuhaler® or Turbuhaler®, which showed that Turbuhaler® gave rise to twice the plasma level of drug as compared with pMDI plus Nebuhaler® [106].…”

Aerosol therapy in childhood asthma

“…A inspiração deve ser rápida e intensa -alto fluxo 81 : em geral são necessários 1 a 2 l/seg (60 a 120 l/min) de fluxo inspiratório para produzir efeito adequado (82); com o Turbuhaler, 0,5 l/seg é suficiente 2,83 , mas se o fluxo inspiratório for maior, de 1 l/seg, os efeitos broncodilatadores serão maiores 84 , refletindo uma melhor deposição pul-monar. Até um certo limite, o aumento do fluxo inspirató-rio aumenta o número de partículas respiráveis, ao contrá-rio do que ocorre com os inaladores pressurizados e dosimetrados 10 .…”

“…A inalação de aerossol gerado por inalador de pó se acompanha de uma significativa deposição de partículas na orofaringe: com o Turbuhaler, cerca de 57% depositam-se na orofaringe 18 e perdem-se na peça bucal em torno de 24% do aerossol gerado 18 , enquanto que, em média, 17% são depositados nos pulmões e 2% retornam com o ar expirado 18 . Por não ser possível usar-se espaçador acoplado aos inaladores de pó, nada se pode fazer para reduzir a taxa de deposição de droga na orofaringe, que representa um componente importante na biodisponibilidade sistêmica das drogas inaladas através desses aparelhos 82 .…”