If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  Dosage Adjustment Not Necessary for Aliskiren in Patients With Hepatic or Renal Impairment: Presented at ACCP By Maria Bishop BOSTON, MA -- September 22, 2006 -- Neither hepatic nor renal impairment had any significant effect on the pharmacokinetics of aliskiren, the first in a new class of novel, orally effective direct renin inhibitors for the treatment of hypertension, researchers reported here at the American College of Clinical Pharmacology 35th Annual Meeting (ACCP). Lead investigator Sujata Vaidyanathan, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, noted that aliskiren is unlikely to exhibit pharmacokinetic interactions with other drugs that are eliminated by pathways involving CYP450 metabolism. This is clinically important, as dose adjustments in this patient group are required for many other antihypertensive drugs (e.g., ACE inhibitors, CCBs and ARBs). Dr. Vaidyanathan's team conducted 2 separate single-center, open-label studies to assess the pharmacokinetics of aliskiren in patients with hepatic impairment and in patients with renal impairment. In the first trial, 16 patients with hepatic impairment were matched for gender, race, age and weight with 16 healthy subjects. Of those who had hepatic impairment, 6 had mild, 6 had moderate and 4 had severe hepatic impairment. A single 300 mg dose of aliskiren was assessed in all participants, measured by plasma concentration-time profiles and pharmacokinetic parameters. The researchers found no correlation between severity of hepatic impairment (Child-Pugh score) and exposure to aliskiren (Cmax and area under the curve). Dose adjustment should, therefore, not be needed in patients with liver disease, Dr. Vaidyanathan noted. In the second trial, 17 males with renal disease and 17 healthy matched controls were assessed for their response to a single dose of 300 mg of aliskiren, examining both pharmacokinetic parameters and safety/tolerability parameters via blood and urine samples. Baseline characteristics were similar. A total of 7 adverse events were reported by 5 subjects (1 healthy, 4 with renal impairment). The most common were headache and diarrhea. All but 1 event were considered mild. Renal impairment was associated with a modest increase in exposure to aliskiren (65% increase in area under the curve); however, changes in exposure did not correlate with creatinine clearance (i.e., severity of the disease). These findings are consistent with an effect of kidney disease on non-renal drug disposition, noted the researchers. Therefore, aliskiren dosage adjustment is not likely to be needed in patients with hypertension and renal impairment, they said.
[Presentation title: Safety, Tolerability and Pharmacokinetics of the Oral Direct Renin Inhibitor Aliskiren in Patients with Hepatic Impairment. Abstract 49. Pharmacokinetics of the Oral Direct Renin Inhibitor Aliskiren in Patients with Renal Impairment. Abstract 50]
|
