title: HMG-COA reductase inhibitors: An opportunity for the improvement of imatinib safety. An experimental study in rat pulmonary hypertension.
abstract: BACKGROUND
  Co-administration of statin with imatinib is thought to result in greater improvement in pulmonary arterial hypertension (PAH) than imatinib treatment alone, and hence may allow greater effectiveness of imatinib therapy at lower doses.
  
  
  METHODS
  The effects of imanitib at dose of 20 and 50mg/kg bw given together with rosuvastatin or simvastatin were investigated with respect to right ventricle pressure (RVP), arterial blood pressure and right ventricle hypertrophy (RVH) in experimental monocrotaline (MCT)-induced pulmonary hypertension. Fourteen days after MCT injection, male rats were treated orally for another 14 days with imatinib, statin or a combination of the two.
  
  
  RESULTS
  Concurrent administration of statin (lipophilic simvastatin, hydrophilic rosuvastatin) and higher dose imatinib reversed the MCT-induced increase in RVP more than each drug alone and decreased RV hypertrophy (RV/LV+S ratio), significantly. The increased RVP and RV hypertrophy was found to be reversed when a lower dose of imatinib was co-administered with rosuvastatin or simvastatin.
  
  
  CONCLUSIONS
  Statins may intensify the beneficial effects of imatinib in PAH, which may be due to the additional influence of statin on the decrease of platelet-derived growth factor (PDGF)-induced effects. These properties allow the dose of imatinib used in PAH treatment to be reduced and thereby might improve its safety profile.
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland. Electronic address: magdalena.jasinska-stroschein@umed.lodz.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jasińska-Stroschein
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Owczarek
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Surowiecka
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kącikowska
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
authors.forename: Daria
authors.initials: D
authors.lastname: Orszulak-Michalak
mesh_terms: D000818:Animals; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000517:prevention & control; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D016686:Monocrotaline; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016686:Monocrotaline; D000068718:Rosuvastatin Calcium; D000068877:Imatinib Mesylate; D019821:Simvastatin
keywords: Combination therapy; HMG-CoA reductase inhibitors; Imatinib; Pulmonary hypertension; Rat