title: Evaluation of the effect of candesartan cilexetil on the steady-state pharmacokinetics of tacrolimus in renal transplant patients.
abstract: BACKGROUND
  Candesartan cilexetil is a possible treatment for hypertension in renal allograft recipients. Tacrolimus is widely used as an immunosuppressant following renal transplantation. The aim of this study was to evaluate the effect of multiple doses of candesartan cilexetil on the steady-state pharmacokinetics of tacrolimus.
  
  
  METHODS
  Twelve patients received oral doses of tacrolimus twice daily for 12 days from study day -2 until day 10, single oral doses of candesartan cilexetil placebo on study days -2 to -1, single oral doses of 2 mg candesartan cilexetil once daily on study days 1 to 3, oral doses of 4 mg candesartan cilexetil once daily on study days 4 to 6, and oral doses of 16 mg candesartan cilexetil once daily on study days 7 to 9. Serial blood samples were collected on days -1, 6 and 9 and were analysed for tacrolimus using microparticle enzyme immunoassay.
  
  
  RESULTS
  Mean C(max,ss) and AUC(tau,ss) values for tacrolimus on day 6 (4 mg candesartan) and day 9 (16 mg candesartan cilexetil) were similar to those on day -1 (tacrolimus alone). Renal function did not change under treatment with candesartan cilexetil compared with baseline. The co-administration of multiple oral doses of cardesartan cilexetil with oral doses of tacrolimus was well tolerated.
  
  
  CONCLUSIONS
  Concomitant administration of multiple doses of candesartan cilexetil does not alter the steady-state pharmacokinetics of tacrolimus.
authors.affiliation: Department of Nephrology and Hypertension, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany. frank.pietruck@uni-essen.de
authors.forename: Frank
authors.initials: F
authors.lastname: Pietruck
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kiel
authors.forename: Manfred
authors.initials: M
authors.lastname: Birkel
authors.forename: Bodo
authors.initials: B
authors.lastname: Stahlheber-Dilg
authors.forename: Thomas
authors.initials: T
authors.lastname: Philipp
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000032:analysis; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007166:Immunosuppressive Agents; D013777:Tetrazoles; D003404:Creatinine; C077793:candesartan cilexetil; D016559:Tacrolimus