Disease relevance of SPP100

• Aliskiren may therefore represent an effective, novel approach to the treatment of hypertension and related disorders, alone or in combination with other antihypertensive agents [1].
• Aliskiren exhibits similar pharmacokinetics in healthy volunteers and patients with type 2 diabetes mellitus [2].
• 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 [3].
• Losartan and aliskiren reduced albuminuria and complement expression [4].

High impact information on SPP100

• Hormonal and BP effects were compared for 48 h after administration of single oral doses of 300 mg (high dose) of the renin inhibitor aliskiren (A300) and 160 mg (standard antihypertensive dose) of the AT1 receptor antagonist valsartan (V160) and their combination each at half dose (A150+V80) in 12 mildly sodium-depleted normotensive individuals [5].
• This study compared the pharmacokinetics and pharmacodynamics of the orally active direct renin inhibitor, aliskiren, in healthy volunteers and patients with type 2 diabetes [2].
• RESULTS: Aliskiren exhibited similar pharmacokinetics in patients with type 2 diabetes and healthy volunteers [2].
• CONCLUSIONS: Aliskiren is an orally effective, long-lasting renin inhibitor that shows antihypertensive efficacy in animals superior to previous renin inhibitors and at least equivalent to angiotensin-converting enzyme inhibitors and AT1-receptor blockers [1].
• OBJECTIVES: Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing [1].

Chemical compound and disease context of SPP100

• Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers [6].
• In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (n=23), ramipril (n=21), or irbesartan (n=23) [7].

Biological context of SPP100

• Aliskiren, a novel, orally effective renin inhibitor, lowers blood pressure in marmosets and spontaneously hypertensive rats [1].
• RESULTS: Aliskiren treatment had no effect on the blood coagulation parameters (PT, INR and aPTT) [8].
• Molecular modeling and X-ray crystallography of the active site of renin have led to the development of new orally active renin inhibitors, such as aliskiren [9].
• SPP 100 has a sufficient bioavailability to induce a sustained blockade of the renin-angiotensin system when given orally to normal subjects [10].
• As aliskiren does not affect cytochrome P450 enzyme activities, is minimally metabolised, and is not extensively protein bound, the potential for drug interactions is predicted to be low [6].

Associations of SPP100 with other chemical compounds

• A single oral dose of 3 mg/kg aliskiren was more effective than the same dose of either remikiren or zankiren, two orally active renin inhibitors previously tested in humans [1].
• CONCLUSIONS: Multiple doses of aliskiren had no detectable effect on the pharmacokinetics or pharmacodynamics of a single dose of warfarin in healthy subjects [8].
• In the cimetidine study (n = 12), aliskiren 150 mg was administered alone or concomitantly with cimetidine 800 mg according to a two-period crossover design [11].
• The antihypertensive effect of aliskiren 150 mg was comparable to that of irbesartan 150 mg (8.9+/-0.7 and 12.5+/-1.2 mm Hg, least-squares reduction in mean sitting DBP and SBP, respectively, for irbesartan) [12].
• Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril [13].

Gene context of SPP100

• While, to date, aliskiren has only been shown to reduce BP, it appears likely that orally-active renin inhibitors could prove useful in the management of a wide range of cardiovascular pathologies [14].

Analytical, diagnostic and therapeutic context of SPP100

• Whether such changes in renin recognition by monoclonal antibodies exist after oral administration of aliskiren, the first orally available renin inhibitor, is not known [15].
• We report the results of animal experiments performed in marmosets and rats in order to characterize aliskiren before its recent investigation in humans [1].
• This open-label, multicenter study compared the pharmacokinetics and safety of the oral direct renin inhibitor aliskiren in 29 elderly (>/=65 years) and 28 young (18-45 years) healthy subjects [16].
• Plasma concentrations of aliskiren and test drugs were determined by liquid chromatography and mass spectrometry methods [11].
• This study investigated the interaction profile of aliskiren, which is of clinical importance because hypertensive patients often require concomitant drug therapy for associated comorbidities [11].

References