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Effect of Verapamil on the Pharmacokinetics of Aliskiren in Healthy Participants
Author(s) -
Rebello Sam,
Leon Selene,
Hariry Sam,
Dahlke Marion,
Jarugula Venkateswar
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010365717
Subject(s) - pharmacokinetics , aliskiren , verapamil , medicine , pharmacology , blood pressure , renin–angiotensin system , calcium
The authors describe the drug‐drug interaction between aliskiren and verapamil in healthy participants. Eighteen participants first received an oral dose of aliskiren 300 mg (highest recommended clinical dose) in period 1. After a 10‐day washout period, the participants received verapamil 240 mg/d for 8 days (period 2). On day 8, the participants also received an oral dose of aliskiren 300 mg. Safety and pharmacokinetic analyses were performed during each treatment period. Concomitant administration of a single dose of aliskiren during steady‐state verapamil resulted in an increase in plasma concentration of aliskiren. The mean increase in AUC 0‐∞ , AUC last , and C max was about 2‐fold. On day 8, in the presence of aliskiren, AUC τ,ss of R‐norverapamil, R‐verapamil, S‐norverapamil, and S‐verapamil was decreased by 10%, 16%, 10%, and 25%, respectively. Similarly, the C max,ss of R‐norverapamil, R‐verapamil, S‐norverapamil, and S‐verapamil was decreased by 13%, 18%, 12%, and 24%, respectively. Aliskiren did not affect the AUC τ,ss ratios of R‐norverapamil/R‐verapamil and S‐norverapamil/S‐verapamil. Aliskiren administered alone or in combination with verapamil was well tolerated in healthy participants. In conclusion, no dose adjustment is necessary when aliskiren is administered with moderate ABCB1 inhibitors such as verapamil (240 mg/d).