Biotransformation of the topical glucocorticoids budesonide and beclomethasone 17α,21-dipropionate in human liver and lung homogenate

Andersson, Paul; Ryrfeldt, Åke

doi:10.1111/j.2042-7158.1984.tb04868.x

Cited by 77 publications

(44 citation statements)

References 9 publications

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“…When given by inhalation, its antiasthmatic effect may be explained by a local pulmonary action [8]. No oxidative or reductive metabolism of budesonide has been noted in human lung homogenates [9]. The drug is rapidly and extensively absorbed [10].…”

Section: Thorsson S Edsbäcker Aamentioning

confidence: 99%

Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer

Thorsson¹,

Edsbäcker²

1998

Eur Respir J

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In the treatment of asthma, inhaled formulations are commonly used to direct drugs to the lungs. The inhaled drug is deposited either in the upper respiratory tract or in the lungs. Exhaled drug generally constitutes a negligible part of the dose. The fraction deposited extrapulmonarily is eventually swallowed and absorbed from the gastrointestinal (GI) tract and will thus contribute to the systemic availability of the inhaled drug.Spacer devices between the actuator and the mouth are used to overcome the problem of co-ordinating actuation and inhalation from a pressurized metered-dose inhaler (pMDI). The particle size in the aerosol is reduced as evaporation of the propellant occurs [1][2][3]. Also, larger particles are preferentially deposited on the walls of the spacer. An increased fraction of small particles means that deposition in the oropharynx is decreased. In addition, lung deposition may be increased due to the fact that the velocity of the aerosol cloud is reduced before inhalation.The Nebuhaler® is a large-volume (750 mL) spacer intended for pMDIs of budesonide and terbutaline sulphate. Studies with 99m Tc-labelled Teflon™ particles, using γ-scintigraphic imaging techniques, have shown that the lung deposition, in asthmatic patients with airflow obstruction, increased from approximately 9% of the metered dose with a pMDI alone, to 21% after a single puff and 15% after multiple puffs when the pMDI was attached to a Nebuhaler® [4]. The lung deposition of 99m Tc-labelled terbutaline sulphate from a pMDI with a Nebuhaler® was 32% compared with 11% from a pMDI alone [5].Scintigraphic imaging is a commonly used technique to determine lung deposition after inhalation. Lung deposition can also be determined from urinary excretion of intact drug, provided that the contribution of orally deposited and subsequently swallowed drug can be accounted for, and that the drug is not metabolized in the lung [6]. One approach to accounting for swallowed drug is to prevent GI absorption by using concomitant oral administration of activated charcoal [7]. Another approach is to calculate the lung deposition from the systemic availability after inhalation by subtracting the estimated oral contribution [7].Budesonide is a potent glucocorticosteroid effective in the treatment of asthma. When given by inhalation, its antiasthmatic effect may be explained by a local pulmonary action [8]. No oxidative or reductive metabolism of budesonide has been noted in human lung homogenates [9]. The drug is rapidly and extensively absorbed [10]. Pharmacokinetic studies, performed in healthy subjects and asthmatic children, have shown that budesonide undergoes a high first-pass metabolism and has a low systemic availability (about 10%) after oral dosing [10,11]. Inhaled budesonide undergoes a rapid systemic uptake, with a time of maximum concentration of about 20 min. The systemic availability was found to be 26% from a pMDI and 38% Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer. L. Thorsson, S. E...

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Section: Thorsson S Edsbäcker Aamentioning

confidence: 99%

Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer

Thorsson¹,

Edsbäcker²

1998

Eur Respir J

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“…The drug is not metabolized in the lung tissue [3], and is rapidly and extensively absorbed [4]. Pharmacokinetic studies, performed in healthy subjects and in asthmatic children, have shown that budesonide has a high hepatic clearance (>1 l·min -1 ) and a high first-pass metabolism, resulting in a low systemic availability (about 10%) after oral dosing [4].…”

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confidence: 99%

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

Thorsson¹,

Edsbäcker²,

Conradson³

1994

Eur Respir J

375

167

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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.

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“…Several transcription factors are involved in this mechanism (CarsonJurica et al 1990;Munk et al 1990;Funder 1993;Barnes and Adcock 1993;Smith and Toft 1993;Barnes 1996). ICS exert their clinical and anti-infl ammatory actions depending on a wide range of variables, including the status of the nasal and bronchial wall (Laitinen 1994;Barnes 1995;Kraft et al 1996), the pharmacodynamic-pharmacokinetic properties of the drug (Andersson and Ryrfeldt 1984;English et al 1994;Miller-Larson et al 1994;Lipworth 1995;Johnson 1996), the delivery system (Brown et al 1990;Selroos and Halme 1991;Smith et al 1995;Pedersen 1996), the patient's cooperation (Toogood et al 1984;Pedersen et al 1986;Lindgren et al 1987;Newman et al 1991), and the dosage regimen (Munch et al 1982;Pincus et al 1995;van Schayck et al 1995;Bernstein et al 2004). These factors also determine the severity and frequency of side-effects (Passalacqua et al 2000).…”

Section: Mechanism Of Action Of Icsmentioning

confidence: 99%

New treatment options in allergic rhinitis: patient considerations and the role of ciclesonide

Braido

Lagasio²,

Piroddi³

et al. 2008

TCRM

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Allergic rhinitis (AR) is a chronic infl ammatory respiratory disease affecting 5%-50% of the worldwide population and its prevalence is increasing (Herman 2007). In addition, AR is associated with asthma and other co-morbidities such as conjunctivitis and sinusitis. The main symptoms are nasal congestion, rhinorrea, sneezing, itching, and post-nasal drainage induced after allergen exposure by an IgE-mediated infl ammation of the membranes lining the nose. AR is not a life-threatening disease, but it has been shown to have a signifi cant impact on quality of life. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines propose a classifi cation of AR in intermittent and persistent, each graded as mild or moderate-severe, and provide a stepwise approach to the treatment. Inhaled steroids and antihistamine are the main tools in AR therapy but more safe and effective drugs are, however, needed. Inhaled steroid ciclesonide appears to be safe and effective.

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Biotransformation of the topical glucocorticoids budesonide and beclomethasone 17α,21-dipropionate in human liver and lung homogenate

Cited by 77 publications

References 9 publications

Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer

Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer

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

New treatment options in allergic rhinitis: patient considerations and the role of ciclesonide

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