Standards for Bioequivalence of Inhaled Products

Chrystyn, Henry

doi:10.2165/00003088-199426010-00001

Cited by 36 publications

(27 citation statements)

References 29 publications

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“…However, as others have emphasized, pharmacokinetic results cannot be directly translated into pharmacodynamic responses [30]. The absence of close correlation is supported by the observation of high intersubject variability in spirometric data.…”

Section: Discussionmentioning

confidence: 95%

Improved delivery of fenoterol plus ipratropium bromide using Respimat® compared with a conventional metered dose inhaler

et al. 2001

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Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) deliveredviaRespimat®, a soft mist inhaler, and to establish the Respimat® dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 µg) which is deliveredviaa conventional metered dose inhaler (MDI).In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 µg deliveredviaRespimat®; F/I 50/20 or 100/40 µg deliveredviaMDI.Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1than placebo. A log-linear dose-response was obtained for the average increase in FEV1up to 6 h (AUC0–6 h) and peak FEV1across the dose range administered by Respimat®. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat® compared with the MDI. However 12.5/5 and 25/10 µg F/I administeredviaRespimat® were closest (slightly superior) to the F/I dose of 100/40 µg deliveredviaMDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat® compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events.In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromideviaRespimat®, is as effective and as safe as higher doses givenviaa metered dose inhaler.

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Section: Discussionmentioning

confidence: 95%

Improved delivery of fenoterol plus ipratropium bromide using Respimat® compared with a conventional metered dose inhaler

et al. 2001

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“…Compared with the MDI the inhalation aid increases were much greater than the intra-individual variability of the urinary excretion method. In 11 individuals who each repeated the same inhalation procedure on four separate occasions, the mean (SD) coefficient of variation was [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] (2-36)%. The mean (SD) 24 hour urinary excretion of salbutamol and its metabolites was 26-6 (6 79), 27'0 (7 95), and 55-6 (9- Inhalation from a static aerosol cloud, from within these devices, reduces particle velocity during inspiration thereby limiting oropharyngeal impaction and systemic absorption.…”

mentioning

confidence: 99%

Relative bioavailability of salbutamol to the lung following inhalation using metered dose inhalation methods and spacer devices.

Hindle

Chrystyn

1994

Thorax

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Inhalation from a static aerosol cloud, from within these devices, reduces particle velocity during inspiration thereby limiting oropharyngeal impaction and systemic absorption. These spacers also overcome the problems of poor coordination and enable an increase in the proportion of the dose delivered to the therapeutically active sites within the lungs.89We have shown that the percentage (amount) of an inhaled dose of salbutamol recovered in a urine sample taken 30 minutes after inhalation is an index of the relative amounts of drug deposited in the respiratory 549 on 10 April 2019 by guest. Protected by copyright.

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“…Also, serum or plasma drug concentrations are low because inhaled doses are small and the volume of distribution is large [24]. inhalation [22].…”

Section: Discussionmentioning

confidence: 99%

Effects of Heat and Humidification on Aerosol Delivery during Auto-CPAP noninvasive Ventilation

Abdelrahim¹

2017

Arch Pulmonol Respir Care

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Objective: Although, the use of humidifi cation during non-invasive ventilation (NIV) is an important factor in decreasing nasal airway resistance and assuring patient's comfort and adherence; many in-vitro studies recommend switching off the humidifi er while delivering aerosol to NIV patients.The aim of the study was to in-vivo determine the effect of humidifi cation on salbutamol delivered via different inhalation devices to chronic obstructive pulmonary disease (COPD) patients using automatic continuous positive airway pressure (Auto-CPAP).Method: Aerosol delivery to NIV COPD patients by Aerogen Solo vibrating mesh nebuliser (VMN), Jet nebuliser (JET) and a metered dose inhaler (MDI) with AeroChamber MV spacer (AC) were compared with and without humidifi cation. Auto-CPAP was adjusted at non-invasive ventilation mode with the integrated heated humidifi er (IHH), as a source of humidity. The heater was set to the default setting 3, equivalent to 50ºC. Urine samples, 30 minutes and 24 hours post inhalation, as an index of the relative pulmonary and systemic bioavailability respectively, were provided by subjects and aliquots were retained for salbutamol analysis using solid phase extraction and high performance liquid chromatography (HPLC). Results:There was no signifi cant difference in the urinary excreted salbutamol post inhalation between the humidifi ed and dry conditions. However, there was a signifi cant difference between devices. The MDI with AC spacer had the highest percentage of 30 minutes urinary excreted salbutamol and JET had the lowest (p<0.01). VMN the highest percentage of 24 hours urinary excreted salbutamol and JET had the lowest but the difference was not signifi cant. Conclusion:Signifi cance of switching off humidity during aerosol delivered to ventilated patient was not as previously shown in in-vitro literatures. We recommend delivering aerosol medication to Auto-CPAP NIV patient using humidity without fear of lower delivery.

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Standards for Bioequivalence of Inhaled Products

Cited by 36 publications

References 29 publications

Improved delivery of fenoterol plus ipratropium bromide using Respimat® compared with a conventional metered dose inhaler

Improved delivery of fenoterol plus ipratropium bromide using Respimat® compared with a conventional metered dose inhaler

Relative bioavailability of salbutamol to the lung following inhalation using metered dose inhalation methods and spacer devices.

Effects of Heat and Humidification on Aerosol Delivery during Auto-CPAP noninvasive Ventilation

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