title: Pharmacokinetics and safety of nifedipine GITS/candesartan fixed-dose combination in subjects with hepatic impairment .
abstract: OBJECTIVE
  To investigate the pharmacokinetic (PK) profiles and safety of nifedipine and candesartan after a single oral dose of nifedipine gastrointestinal therapeutic system (GITS) 30 mg/candesartan cilexetil 8 mg (N30/C8 mg) fixed-dose combination (FDC) in adults with mild to moderate hepatic impairment.
  
  
  METHODS
  A phase I, single-center, non-randomized, non-controlled, non-blinded, observational study (N = 32). PK profiles for nifedipine and candesartan were assessed in patients with mild (Child-Pugh A; group 1) or moderate (Child-Pugh B; group 2) hepatic impairment and compared with age- and gender-matched healthy controls (groups 3 and 4) following a single dose of N30/C8 FDC. Safety and tolerability were assessed throughout the study.
  
  
  RESULTS
  On average, area under the plasma concentration vs. time curves (AUC) for nifedipine increased 93% and 253% in mild and moderate hepatic impairment, while maximum plasma concentrations (Cmax) increased 64% and 171%, respectively. AUC values for candesartan increased 19% and 92%, while Cmaxvalues increased 3% and 11%, respectively. In subjects with or without liver impairment, adverse event rates were similar and consistent with the known side-effect profiles of nifedipine GITS and candesartan as monotherapies.
  
  
  CONCLUSIONS
  Careful monitoring, and, if necessary, dose adjustment according to response and tolerability may be required for nifedipine GITS/candesartan FDC in patients with mild and moderate hepatic impairment. .
authors.forename: Yuwang
authors.initials: Y
authors.lastname: Liu
authors.forename: Michael-Friedrich
authors.initials: MF
authors.lastname: Boettcher
authors.forename: Anja
authors.initials: A
authors.lastname: Schmidt
authors.forename: Sigrun
authors.initials: S
authors.lastname: Unger
authors.forename: Atef
authors.initials: A
authors.lastname: Halabi
authors.forename: Erich
authors.initials: E
authors.lastname: Brendel
authors.forename: Hartmut
authors.initials: H
authors.lastname: Blode
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D005858:Germany; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008107:Liver Diseases / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012720:Severity of Illness Index; D013607:Tablets; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D013607:Tablets; D014665:Vasodilator Agents; D009543:Nifedipine