ArticleClinical pharmacokinetics2013
Characterizing systemic exposure of inhaled drugs: application to the long-acting β2-agonist PF-00610355.
Article in Clinical pharmacokinetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Targeting SARS-CoV-2 nsp13 Helicase and Assessment of Druggability Pockets: Identification of Two Potent Inhibitors by a Multi-Site In Silico Drug Repurposing Approach.Molecules (Basel, Switzerland) · 2022Article
- Inferring pulmonary exposure based on clinical PK data: accuracy and precision of model-based deconvolution methods.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Screening of drug databank against WT and mutant main protease of SARS-CoV-2: Towards finding potential compound for repurposing against COVID-19.Saudi journal of biological sciences · 2021Article
- Developing inhaled protein therapeutics for lung diseases.Molecular biomedicine · 2020Review
- Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs.The AAPS journal · 2015Review
- Predicted heart rate effect of inhaled PF-00610355, a long acting β-adrenoceptor agonist, in volunteers and patients with chronic obstructive pulmonary disease.British journal of clinical pharmacology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesPF-00610355 is an orally inhaled long-acting β2-adrenoreceptor agonist that is being developed for the once-daily treatment of chronic obstructive pulmonary disease (COPD). The pharmacological effect is exerted in the lungs. However, systemic exposure of PF-00610355 is expected to be responsible for certain drug-related adverse effects. This analysis characterizes PF-00610355 using an integrated analysis of systemic exposure, across trials and patient populations.
methodsA total of 6,107 samples of PF-00610355 plasma concentration, collected in 264 subjects from eight studies in healthy volunteers, asthma, and COPD patients, were analyzed using non-linear mixed-effects models. Model-based mean (95 % CI) exposure profiles for a range of PF-00610355 doses in COPD patients were simulated.
resultsPF-00610355 exposure profiles were described by a three-compartment disposition model with first-order absorption through a transit compartment. Patient status, inhalation device, and demographic factors were found to influence systemic drug exposure. Relative fine particle dose had a minor effect, whereas no effect of baseline lung function on the systemic exposure was found. An implicit method to address pharmacokinetic variability between occasions of drug intake yielded similar results as the established explicit method, yet in a much more efficient way.
conclusionThe estimated systemic pre-dose and maximum PF-00610355 plasma concentration was 23 and 38 % in COPD patients compared to healthy volunteers, respectively. The analysis illustrated the value of an integrated pharmacokinetic analysis to address specific challenges in the clinical development of long-/ultra-long-acting β2-agonists and inhaled compounds in general, both in relation to selecting a safe starting dose in patients, but also in understanding exposure and systemic safety information across different patient populations and different inhalation devices/formulations.
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