Effect of verapamil on the pharmacokinetics of aliskiren in healthy participants.
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).
Rebello
Sam
S
Novartis Institute for Biomedical Research, One Health Plaza, Bldg 438-3410, East Hanover, NJ 07936-1080, USA. sam.rebello@novartis.com
Leon
Selene
S
Hariry
Sam
S
Dahlke
Marion
M
Jarugula
Venkateswar
V
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000577:Amides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D004347:Drug Interactions; D005650:Fumarates / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D014700:Verapamil / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000577:Amides; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D005650:Fumarates; C446481:aliskiren; C016904:norverapamil; D014700:Verapamil