title: Pharmacokinetic drug-drug interaction of calcium channel blockers with cyclosporine in hematopoietic stem cell transplant children.
abstract: BACKGROUND
  Cyclosporine (CsA) is frequently responsible for hypertension in bone marrow transplant children. Calcium channel blockers (CCBs) are considered to be the best treatment for CsA-induced hypertension, but they may alter the exposure and the effect of CsA by inhibiting the CYP3A4 pathway of CsA metabolism or P-gp. However, the inhibitory effect on CYP3A4 may vary among CCBs.
  
  
  METHODS
  This study aimed to quantify the pharmacokinetic drug-drug interaction between CsA and nicardipine, amlodipine, and lacidipine. In all, 51 children who received CsA and CCB concomitantly were included.
  
  
  RESULTS
  Dose-normalized CsA trough blood concentrations significantly increased in patients treated with nicardipine and amlodipine, whereas they remained stable in patients treated with lacidipine.
  
  
  CONCLUSIONS
  Because lacidipine appears to have no effect on CsA exposure, it may be the best option among CCBs for treating high blood pressure caused by CsA in children.
authors.affiliation: Institut d'Hématologie et d'Oncologie Pédiatrique, Lyon, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Bernard
authors.affiliation: Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, Villeurbanne, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Goutelle
authors.affiliation: Institut d'Hématologie et d'Oncologie Pédiatrique, Lyon, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.affiliation: Institut d'Hématologie et d'Oncologie Pédiatrique, Lyon, France Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, Villeurbanne, France nathalie.bleyzac@chu-lyon.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bleyzac
mesh_terms: D000293:Adolescent; D017311:Amlodipine / Q000493:pharmacokinetics / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000009:adverse effects / Q000493:pharmacokinetics*; D004095:Dihydropyridines / Q000493:pharmacokinetics / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D007223:Infant; D008297:Male; D009529:Nicardipine / Q000493:pharmacokinetics / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007166:Immunosuppressive Agents; D017311:Amlodipine; C060285:lacidipine; D016572:Cyclosporine; D009529:Nicardipine
keywords: bone marrow transplantation; calcium-channel blockers; cyclosporine; drug interactions; pediatrics