Document Detail


Pharmacokinetics of aliskiren in patients with end-stage renal disease undergoing haemodialysis.
MedLine Citation:
PMID:  23018529     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Dmytro Khadzhynov; Torsten Slowinski; Ina Lieker; Hans-Hellmut Neumayer; Diego Albrecht; Henk Johan Streefkerk; Sam Rebello; Harm Peters
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical pharmacokinetics     Volume:  51     ISSN:  0312-5963     ISO Abbreviation:  Clin Pharmacokinet     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7606849     Medline TA:  Clin Pharmacokinet     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  661-9     Citation Subset:  IM    
Affiliation:
Department of Nephrology, Charité Universitätsmedizin Berlin, Humboldt University, Charité Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany.
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