+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Model-based evaluation of pulmonary pharmacokinetics in asthmatic and COPD patients after oral olodaterol inhalation



Model-based evaluation of pulmonary pharmacokinetics in asthmatic and COPD patients after oral olodaterol inhalation



British Journal of Clinical Pharmacology 82(3): 739-753



Olodaterol is an orally inhaled β2 -agonist for treatment of chronic obstructive pulmonary disease (COPD). The aims of this population pharmacokinetic (PK) analysis were: (1) to investigate systemic PK and thereby make inferences about pulmonary PK in asthmatic patients, COPD patients and healthy volunteers, and (2) to assess whether differences in pulmonary efficacy might be expected based on pulmonary PK characteristics. Plasma and urine data after olodaterol inhalation were available from six clinical trials comprising 710 patients and healthy volunteers (single and multiple dosing). To investigate the relevance of covariates, full fixed-effect modelling was applied based on a previously developed healthy volunteer systemic disposition model. A pulmonary model with three parallel absorption processes best described PK after inhalation in patients. The pulmonary bioavailable fraction (PBIO) was 48.7% (46.1-51.3%, 95% confidence interval) in asthma, and 53.6% (51.1-56.2%) in COPD. In asthma 87.2% (85.4-88.8%) of PBIO was slowly absorbed with an absorption half-life of 18.5 h (16.3-21.4 h), whereas in COPD 80.1% (78.0-82.2%) was absorbed with a half-life of 37.8 h (31.1-47.8 h). In healthy volunteers absorption was faster, with a half-life of 18.5 h (16.3-21.4 h) of the slowest absorbed process, which characterized 74.6% (69.1-80.2%) of PBIO. The modelling approach successfully described data after olodaterol inhalation in patients and healthy volunteers. Slow pulmonary absorption was demonstrated both in asthma and COPD. Absorption characteristics after olodaterol inhalation indicated even more beneficial lung targeting in patients compared to healthy volunteers.

(PDF emailed within 0-6 h: $19.90)

Accession: 058327736

Download citation: RISBibTeXText

PMID: 27145733

DOI: 10.1111/bcp.12999


Related references

Long-term outcome of a day-hospital based pulmonary rehabilitation programme in asthmatic and COPD patients. European Respiratory Journal 12(SUPPL 28): 3S, Sept, 1998

Attitudes of Hungarian asthmatic and COPD patients affecting disease control: empirical research based on Health Belief Model. Frontiers in Pharmacology 4: 135, 2013

Pharmacokinetics of andolast after administration of single escalating doses by inhalation in mild asthmatic patients. Biopharmaceutics & Drug Disposition 22(2): 73-81, 2001

Long-term evaluation of home-based pulmonary rehabilitation in patients with COPD. International Journal of Chronic Obstructive Pulmonary Disease 10: 2037-2044, 2016

Comparison of oral theophylline and salbutamol by inhalation in asthmatic patients. British Journal of Clinical Pharmacology 3(4): 591-594, 2012

Evaluation of the effects of olodaterol on exercise endurance in patients with chronic obstructive pulmonary disease: results from two 6-week crossover studies. Respiratory Research 17(1): 77, 2017

Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach. British Journal of Clinical Pharmacology 81(3): 538-552, 2016

Pharmacokinetics of oral theophylline in asthmatic children: evaluation of a new preparation, "Theolair". Annals of Allergy 40(3): 167-170, 1978

The development of an integrated care model for patients with severe or very severe chronic obstructive pulmonary disease (COPD): the COPD-Home model. Scandinavian Journal of Caring Sciences 28(3): 469-477, 2016

Pharmacokinetics of nebulized and oral procaterol in asthmatic and non-asthmatic subjects in relation to doping analysis. Drug Testing and Analysis 8(10): 1056-1064, 2016

Evaluation of a novel breath activated inhalation device in asthmatic patients. European Respiratory Journal 7(SUPPL 18): 52S, 1994

Pharmacokinetics of oral theophylline. Comparison between asthmatic and cystic fibrosis patients. La Pediatria Medica E Chirurgica 7(6): 823-825, 1985

Effects of amphotericin B gargles on oral colonization of Candida albicans in asthmatic patients on steroid inhalation therapy. Respiration; International Review of Thoracic Diseases 68(5): 465-470, 2001

Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO ® and OTEMTO ® studies: a subgroup analysis by age. International Journal of Chronic Obstructive Pulmonary Disease 11: 2701-2710, 2017

Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. International Journal of Chronic Obstructive Pulmonary Disease 9: 629-645, 2015