title: In Silico comparison between metoprolol succinate and bisoprolol on 24-hour systolic blood pressures.
abstract: 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).
  
  
  CONCLUSIONS
  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.affiliation: AstraZeneca R&D, Pepparedsleden 1, 431 83, Mölndal, Sweden, Sven-Olof.Jansson@AstraZeneca.com.
authors.forename: Sven-Olof
authors.initials: SO
authors.lastname: Jansson
authors.forename: Anders E
authors.initials: AE
authors.lastname: Malm
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lundström
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D017298:Bisoprolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000494:pharmacology; D006801:Humans; D008790:Metoprolol / Q000494:pharmacology*; D008954:Models, Biological
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D008790:Metoprolol; D017298:Bisoprolol