Document Detail


In Silico Comparison Between Metoprolol Succinate and Bisoprolol on 24-Hour Systolic Blood Pressures.
MedLine Citation:
PMID:  25488798     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: To compare the effects of bisoprolol and metoprolol CR/ZOK (metoprolol succinate controlled release) on systolic blood pressure (bpsys) over a 24-h period in an in silico model.
METHODS: On the basis of the observed data from ambulatory blood pressure measurements (ABPM), a model with an appropriate distribution and correlation structure was derived for simulation of 24-h bpsys patterns during treatment with commonly studied doses, assumed to be equipotent, of bisoprolol and metoprolol CR/ZOK. Input into the simulations was aligned with the available data on the diurnal efficacy and pharmacology profiles of these substances. The validity of the model was tested in a bootstrap model.
RESULTS: The simulation model reproduced the observed data with high congruence (p = 1.0). The mean 24-h bpsys values did not significantly differ between the two simulated groups (estimated overall change in bpsys [∆bpsys] for metoprolol versus bisoprolol = 2.7 mmHg [95 % confidence interval -0.3 to 5.7 mmHg]; p = 0.08). There were clear diurnal differences, with bisoprolol being more effective earlier and metoprolol CR/ZOK being more effective later in the 24-h day. A validity test with 100 repeated samples gave an overall mean group difference of 1.4 ± 3.59 mmHg (p = 0.63 relative to simulation).
CONCLUSION: In a robust model for the simulation of 24-h ABPM, comparisons between bisoprolol and metoprolol CR/ZOK indicate a comparable overall blood pressure-lowering effect but different diurnal patterns, consistent with the pharmacokinetics of the two drugs. This difference may be of clinical relevance, given the recognized diurnal pattern of cardiovascular events.
Authors:
Sven-Olof Jansson; Anders E Malm; Torbjörn Lundström
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-9
Journal Detail:
Title:  Drugs in R&D     Volume:  -     ISSN:  1179-6901     ISO Abbreviation:  Drugs R D     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-9     Completed Date:  -     Revised Date:  2014-12-10    
Medline Journal Info:
Nlm Unique ID:  100883647     Medline TA:  Drugs R D     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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