title: Pharmacokinetics, safety, and tolerability of the oral Renin inhibitor aliskiren in patients with hepatic impairment.
abstract: Aliskiren is the first in a new class of orally active, direct renin inhibitors for the treatment of hypertension. This open-label, nonrandomized, single-center, parallel-group study compared the pharmacokinetics and safety of a single 300-mg oral dose of aliskiren in patients with mild, moderate, or severe hepatic impairment to that in healthy subjects. When pooled across subgroups, there were no significant differences between patients with hepatic impairment and healthy subjects in aliskiren AUC(0-infinity) (ratio of geometric means, 1.12; 90% confidence interval, 0.85, 1.48) or Cmax (mean ratio, 1.19; 90% confidence interval, 0.84, 1.68), and there was no correlation between severity of hepatic impairment and either AUC(0-infinity) or Cmax. Aliskiren was well tolerated by healthy subjects and patients with hepatic impairment. In conclusion, hepatic impairment has no significant effect on the pharmacokinetics of aliskiren following single-dose administration, and dosage adjustment is unlikely to be needed in patients with liver disease.
authors.affiliation: Novartis Institute for Biomedical Research, 400 Technology Square, Building 605-820, Cambridge, MA 02139, USA.
authors.forename: Sujata
authors.initials: S
authors.lastname: Vaidyanathan
authors.forename: Vance
authors.initials: V
authors.lastname: Warren
authors.forename: Chingming
authors.initials: C
authors.lastname: Yeh
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Bizot
authors.forename: Hans Armin
authors.initials: HA
authors.lastname: Dieterich
authors.forename: William P
authors.initials: WP
authors.lastname: Dole
mesh_terms: D000577:Amides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005650:Fumarates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren