Abstract：
: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.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Rebello S,Compain S,Feng A,Hariry S,Dieterich HA,Jarugula Vdoi
10.1177/0091270010385934subject
Has Abstractpub_date
2011-11-01 00:00:00pages
1549-60issue
11eissn
0091-2700issn
1552-4604pii
0091270010385934journal_volume
51pub_type
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