Intra-Subject Variability in Lung Dose in Healthy Volunteers Using Five Conventional Portable Inhalers

Aswania, Osama; Ritson, S; Iqbal, S.M.; Bhatt, Jayesh; Rigby, Alan S.; Everard, Mark L.

doi:10.1089/0894268042176346

Cited by 6 publications

(6 citation statements)

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“…Interindividual variation in serum concentrations was remarkable and corresponds with literature on DPI [27,28,39,40]. The population in this study consisted of CF patients in different conditions regarding FEV1 (range 32-104%) and this may have contributed to the observed range of serum concentrations.…”

Section: Discussionsupporting

confidence: 79%

Dry powder inhalation of colistin in cystic fibrosis patients: A single dose pilot study

Westerman

Boer

Brun

et al. 2007

Journal of Cystic Fibrosis

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Section: Discussionsupporting

confidence: 79%

Dry powder inhalation of colistin in cystic fibrosis patients: A single dose pilot study

Westerman

Boer

Brun

et al. 2007

Journal of Cystic Fibrosis

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“…Such variance has to be minimized in order to detect any difference between inhalers. Intrasubject variation between breaths is in the region of 8–10% for highly trained volunteers, but 32–52% for those given initial training only [23–28]. With adequate training, differences in fine particle dose for the same product are detectable with only a few volunteers [29].…”

Section: Chemisimilars: Inhalers As Exemplarsmentioning

confidence: 99%

Generics, chemisimilars and biosimilars: is clinical testing fit for purpose?

Warren

2012

Brit J Clinical Pharma

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The effectiveness and safety of generic drugs are backed by sound physicochemical control and regulatory bioequivalence acceptance criteria. Statistical testing of bioequivalence, comparing the pharmacokinetic profiles of the test and reference products, was made possible by modern drug assays. When the pharmacokinetic profile correlates with the dose, such comparisons show assay sensitivity and readily detect differences in dose. For large biological molecules, different manufactured batches cannot be validated using pharmacokinetic data alone. For these biosimilars, there is a three-stage assessment of pharmaceutical quality, laboratory testing and clinical data. This approach has also been applied to certain chemical products, termed 'chemisimilars' , which have variable or complex synthesis of the active substance, or complex formulation, or a complex delivery device. Although there may be no detectable difference between the test and reference on clinical testing, many of the outcome measures are insensitive to even large differences in dose. For testing to be fit for purpose it should distinguish important dose differences, but many clinical tests of chemisimilars and biosimilars do not. As pharmacokinetic and pharmacodynamic technology advances, the trend of replacing dose-insensitive clinical trial data with equivalence tests that show assay sensitivity can be expected to continue.

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“…As pointed out by Telko and Hickey, “there are many more ways to administer an inhaled aerosol than there are to swallow a tablet.” Variability within a patient and among a group of patients can be high . As a result, a key goal with inhaled aerosols is to achieve consistent drug delivery to the lungs.…”

Section: Product Design Considerationsmentioning

confidence: 99%