Pharmacokinetics of Aliskiren in Patients with End-Stage Renal Disease Undergoing Haemodialysis

Background and Objectives 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. Conclusion 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.