Pharmacokinetics, safety, and tolerability of the novel oral direct renin inhibitor aliskiren in elderly healthy subjects.
This open-label, multicenter study compared the pharmacokinetics and safety of the oral direct renin inhibitor aliskiren in 29 elderly (>or=65 years) and 28 young (18-45 years) healthy subjects. Plasma drug concentrations were determined for up to 168 hours following a single 300-mg oral dose of aliskiren. In elderly compared with young subjects, AUC(0-infinity) was 57% higher (ratio of geometric means 1.57, 90% confidence interval: 1.19, 2.06; P = .008) and C(max) was 28% higher (1.28, 90% confidence interval: 0.91, 1.79; P=.233). Other parameters, including t(max) and Vd/F, were similar between age groups. No differences in aliskiren exposure were observed between subjects ages 65 to 74 years (n=16) and >or=75 years (n=13). Aliskiren was well tolerated by all age groups, including the very elderly. In conclusion, aliskiren exposure is modestly increased in elderly subjects. Based on its wide therapeutic index and shallow dose response for blood pressure lowering, no initial dose adjustment should be needed for elderly patients.
Vaidyanathan
Sujata
S
Novartis Fharmaceuticals Corporation, East Hanover, New Jersey, USA.
Reynolds
Christine
C
Yeh
Ching-Ming
CM
Bizot
Marie-Noëlle
MN
Dieterich
Hans Armin
HA
Howard
Dan
D
Dole
William P
WP
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000577:Amides / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D005650:Fumarates / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000092502:Renin Inhibitors
D000577:Amides; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren