Effect of cyclosporine on the pharmacokinetics of aliskiren in healthy subjects

J Clin Pharmacol. 2011 Nov;51(11):1549-60. doi: 10.1177/0091270010385934. Epub 2011 Mar 15.


To explore the clinical relevance of inhibition of multidrug resistance transporter 1 and organic anion transporting polypeptide transporter, a drug-drug interaction study was conducted using aliskiren and cyclosporine. This was an open-label, single-sequence, parallel-group, single-dose study in healthy subjects. Subjects (n = 14) first received aliskiren 75 mg orally (period 1), followed by aliskiren 75 mg + cyclosporine 200 mg (period 2) after a 7-day washout period, and aliskiren 75 mg + cyclosporine 600 mg (period 3) after a 14-day washout period. Safety and pharmacokinetics were analyzed during each period. The primary objective was to characterize pharmacokinetics of aliskiren (single-dose and combination with cyclosporine). The increases in area under the time-concentration curve from time 0 to infinity and maximum concentration associated with cyclosporine 200 mg or 600 mg were 4- to 5-fold and 2.5-fold, respectively. Mean half-life increased from 25 to 45 hours. Based on comparison to literature, a single-dose of aliskiren 75 mg did not alter the pharmacokinetics of cyclosporine. Aliskiren 75 mg was well tolerated. Combination with cyclosporine increased the number of adverse events, mainly hot flush and gastrointestinal symptoms, with no serious adverse events. Two adverse events led to withdrawal (ligament rupture, not suspected to be study-drug related; and vomiting, suspected to be study-drug related). Laboratory parameters, vital signs, and electrocardiographs showed no time- or treatment-related changes. As cyclosporine significantly altered the pharmacokinetics of aliskiren in humans, its use with aliskiren is not recommended.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Administration, Oral
  • Adult
  • Amides / adverse effects
  • Amides / pharmacokinetics*
  • Area Under Curve
  • Cyclosporine / adverse effects
  • Cyclosporine / pharmacokinetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inhibitors
  • Drug Interactions
  • Female
  • Fumarates / adverse effects
  • Fumarates / pharmacokinetics*
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Organic Anion Transporters / antagonists & inhibitors
  • Organic Anion Transporters / metabolism
  • Young Adult


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Amides
  • Cytochrome P-450 CYP3A Inhibitors
  • Fumarates
  • Organic Anion Transporters
  • aliskiren
  • Cyclosporine
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human