Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI

Abstract

L Lu un ng g d de ep po os si it ti io on n o of f b bu ud de es so on ni id de e f fr ro om m T Tu ur rb bu uh ha al le er r¤ ¤ i is s t tw wi ic ce e t th ha atABSTRACT: The pulmonary and systemic availability of budesonide after inhalation from a dry powder inhaler, Turbuhaler®, and from a pressurized metered-dose inhaler (P-MDI) were compared in healthy volunteers. Two different methods were used to assess pulmonary availability: 1) calculated from the systemic availability corrected for an oral availability of 13% (n=24); and 2) after blocking of gastrointestinal absorption by administration of a charcoal suspension (n=13). An intravenous infusion of budesonide was used as a reference.The systemic availability of budesonide, calculated as a geometric mean and expressed as percentage of the metered dose, was 38% for Turbuhaler® and 26% for P-MDI. The pulmonary availability, calculated using the first method, was 32% and 15% for Turbuhaler® and P-MDI, respectively; and, using the second method, 32% and 18%, respectively.The results of the present study indicate that administration of budesonide via Turbuhaler® gives rise to a lung deposition which is approximately twice that of a P-MDI, with less variability, but that systemic availability is only increased by approximately 50%. Thus, the present data suggest that by administrating budesonide via Turbuhaler®, instead of a P-MDI, the same degree of asthma control can be achieved with a lower dose, which, in turn, reduces the risk of undesired systemic effects.

Pharmacokinetics and systemic activity of fluticasone via Diskus® and pMDI, and of budesonide via Turbuhaler®

“…Hence, the fate within the lung of this fraction, which eventually determines the extent and duration of pharmacological activity, cannot be deduced from plasma determinations of MAT, as has been implied by some investigators [19]. The elimination half-life of budesonide was close to 5 h in the present study, which is longer than the 2±3 h found in earlier studies [2,10]. This discrepancy is likely due to shorter sampling times and a lower sensitivity in the Tables 4a and 4b Pharmacokinetic parameters derived from repeated dose inhalations (1000 mg twice daily) of budesonide via Turbuhaler and of uticasone via pMDI and Diskus.…”

“…This discrepancy between single and repeated dosing for cortisol suppression may be explained by the pharmacokinetic properties of the drugs, since¯uticasone has been found to have a slower systemic elimination than budesonide, leading to accumulation and doubling of plasma concentrations after repeated dosing [3]. The elimination half-life of¯utica-sone is considerably longer than for many other inhaled corticosteroids; elimination half-lives in the range of 1.5±2.5 h have been reported for triamcinolone acetonide [8],¯unisolide [9], and budesonide [10]. Thus, an extensive distribution into tissues, as indicated by a high volume of distribution, appears to be the cause of this slow elimination of¯uticasone.…”

“…Available documentation on pharmacokinetics and systemic effects of¯uticasone and budesonide is mainly based on studies in healthy subjects [1,5,6,10,11]. One reason for this is to minimize the between-subject variability [12].…”

Inhaled Glucocorticoids for Asthma

“…For example, a multiple dry-powder delivery system, the Turbuhaler, delivers approximately twice as much glucocorticoid to the lungs as other devices, but requires only half as large a dose. 60 …”

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

“…Turbuhaler® has been thoroughly investigated with respect to lung deposition, and the general picture is that about 20-30% of the dose reaches the lung, both in healthy volunteers and in patients, at an inhalation flow of approximately 60 L·min -1 [41,47,51,52,57,67,68]. At a low inhalation flow, approximately 30 L·min -1 , lung deposition was lower than at a flow of 60 L·min -1 , but similar to that after a well-performed inhalation from the corresponding pMDI.…”