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Pharmacokinetics of Aliskiren in Patients with End-Stage Renal Disease undergoing Hemodialysis

Rebello, Sam and Albrecht, Diego and Streefkerk, Hendrik (2012) Pharmacokinetics of Aliskiren in Patients with End-Stage Renal Disease undergoing Hemodialysis. Clinincal Pharmacokinetics, 51 (10). pp. 661-669. ISSN 0312-5963

Abstract

Background: Aliskiren represents a novel class of orally active renin inhibitors. The present study analyses pharmacokinetics, tolerability and safety of single dose aliskiren in End Stage Renal Disease (ESRD) patients undergoing hemodialysis (HD).
Methods: Six ESRD patients and six matched healthy volunteer 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 h or 1 h before the a standardized HD session (4 h, 1.4 m2 high-flux filter, blood flow 300ml/min, dialysate flow 500ml/min). Wash out was >10 days between both periods. Blood and dialysis samples were taken for up to 96 h post-dose to determine aliskiren concentrations. The healthy subjects received aliskiren 300mg single dose with 96 h plasma pharmacokinetics.
Results: Compared to the healthy subjects (1681±1034 ng*h/mL), the AUCinf was 61% (HD at 48h) and 41% (HD at 1h) higher in ESRD patients receiving single dose 300 mg aliskiren. Cmax (481±497 ng/ml in healthy subjects) was 17% higher (HD at 48h) und 16% lower (HD at 1h), respectively. In both treatment periods, dialysis clearance was below 2% of oral clearance and mean fraction eliminated from circulation below 13%. Drug AUC´s were similar in ESRD patients receiving aliskiren 1 or 48 hours before dialysis. No severe adverse reactions occurred.
Conclusions: Aliskiren´s drug exposure is moderately higher in ESRD patients. Only a minor portion is removed by a typical HD session. Aliskiren drug exposure is not significantly affected by intermittent hemodialysis. Based on these results, no dose adjustment is warranted in ESRD patients receiving hemodialysis.

Item Type: Article
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Keywords: aliskiren, pharmacokinetics, end-stage renal disease, intermittent hemodialysis
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/3275

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