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Predicted Heart Rate Effect of Inhaled LABA PF-00610355 in volunteers and COPD patients.
MedLine Citation:
PMID:  23323609     Owner:  NLM     Status:  Publisher    
AIM: To assess the cardiovascular effects of a new inhaled long-acting beta agonist PF-00610355 in COPD Patients. METHODS: 13,062 heart rate measurements collected in 10 clinical studies from 579 healthy volunteers, asthma, and COPD patients, were analyzed. The relationship between heart rate profiles and predicted plasma concentration profiles, patient status, demographics, and concomitant medication was evaluated using non-linear mixed-effects models. The median heart rate increase in COPD patients for doses of PF-00610355 up to 280 μg QD was simulated with the final pharmacokinetics/pharmacodynamics (PKPD) model. RESULTS: An EMAX model accounting for delayed on- and offset of the PF-00610355-induced change in heart rate was developed. The predicted potency in COPD patients was 3-fold lower compared to healthy volunteers, while no difference in maximum drug effect was identified. Simulations suggested a maximum placebo-corrected increase of 2.7 (0.90-4.82) bpm in COPD patients for a PF-00610355 dose of 280 μg QD, with 19% subjects experiencing a heart rate increase of more than 20 bpm compared to 8% in the placebo group. CONCLUSIONS: This PKPD analysis supports the clinical observation that no relevant effects of PF-00610355 on heart rate in COPD patients should be expected for doses up to 280 μg QD.
Paul Matthias Diderichsen; Eugène Cox; Steven W Martin; Adriaan Cleton; Jakob Ribbing
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  -     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.
Quantitative Solutions BV, The Netherlands.
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