title: Pharmacokinetics of aliskiren in patients with end-stage renal disease undergoing haemodialysis.
abstract: OBJECTIVE
  Aliskiren represents a novel class of orally active renin inhibitors. This study analyses the pharmacokinetics, tolerability and safety of single-dose aliskiren inpatients with end-stage renal disease (ESRD) undergoing haemodialysis.
  
  
  METHODS
  Six ESRD patients and six matched healthy volunteers were enrolled in an open-label, parallel-group, single-sequence study. The ESRD patients underwent two treatment periods where 300 mg of aliskiren was administered 48 or 1 h before a standardized haemodialysis session (4 h, 1.4 m(2) high-flux filter, blood flow 300 mL/min, dialysate flow 500 mL/min). Washout was >10 days between both periods. Blood and dialysis samples were taken for up to 96 h postdose to determine aliskiren concentrations.
  
  
  RESULTS
  Compared with the healthy subjects (1681 ± 1034 ng·h/mL), the area under the plasma concentration-time curve (AUC) from time zero to infinity was 61% (haemodialysis at 48 h) and 41% (haemodialysis at 1 h) higher in ESRD patients receiving single-dose aliskiren 300 mg. The maximum (peak) plasma drug concentration (481 ± 497 ng/mL in healthy subjects) was 17% higher (haemodialysis at 48 h) and 16% lower (haemodialysis at 1 h). In both treatment periods, dialysis clearance was below 2% of oral clearance and the mean fraction eliminated from circulation was 10 and 12% in period 1 and 2, respectively. Drug AUCs were similar in ESRD patients receiving aliskiren 1 or 48 h before dialysis. No severe adverse events occurred.
  
  
  CONCLUSIONS
  The exposure of aliskiren is moderately higher in ESRD patients. Only a minor portion is removed by a typical haemodialysis session. Aliskiren exposure is not significantly affected by intermittent haemodialysis, suggesting that no dose adjustment is necessary in this population.
authors.affiliation: Department of Nephrology, Charité Universitätsmedizin Berlin, Humboldt University, Charité Campus Mitte, Berlin, Germany.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Khadzhynov
authors.forename: Torsten
authors.initials: T
authors.lastname: Slowinski
authors.forename: Ina
authors.initials: I
authors.lastname: Lieker
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Diego
authors.initials: D
authors.lastname: Albrecht
authors.forename: Henk Johan
authors.initials: HJ
authors.lastname: Streefkerk
authors.forename: Sam
authors.initials: S
authors.lastname: Rebello
authors.forename: Harm
authors.initials: H
authors.lastname: Peters
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D005650:Fumarates; D007004:Hypoglycemic Agents; D000092502:Renin Inhibitors; C446481:aliskiren