Reference

Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in japanese and Caucasian subjects

All Rights Reserved. Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in japanese and Caucasian subjects. Vaidyanathan, Sujata; Jermany, Joanne; Yeh, ChingMing; Bizot, Marie-Noelle; Camisasca, Riccardo (Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA). British Journal of Clinical Pharmacology, 62(6), 690-698 (English) 2006 Blackwell Publishing Ltd. CODEN: BCPHBM. ISSN: 0306-5251. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Aims: Aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension. This study compared the pharmacokinetic and pharmacodynamic properties of aliskiren in Japanese and Caucasian subjects. Methods: In this open-label, single-center, parallel-group, single- and multiple-dose study, 19 Japanese and 19 Caucasian healthy young male subjects received a single 300-mg oral dose of aliskiren on day 1 and then aliskiren 300 mg once daily on days 4-10. Blood samples were collected for the measurement of plasma aliskiren concn., plasma renin concn. (PRC) and plasma renin activity (PRA). Results: Pharmacokinetic parameters were comparable in Japanese and Caucasian subjects following administration of a single dose of aliskiren (ratio of geometric means: Cmax 1.12 [90% confidence interval Cl) 0.88, 1.43]; AUC0-72 h 1.19 [90% Cl 1.02, 1.39] and at steady state mean ratio: Cmax 1.30 (90% Cl 1.00, 1.70); AUC0-t 1.16 (90% Cl 0.95, 1.41). There was no notable difference in the plasma half-life of aliskiren between Japanese and Caucasian groups (29.7 ± 10.2 h and 32.0 ± 6.6 h, resp. 9015-94-5 and 173334-57-1 are also in the experiment.). At steady state, peak PRC level and AUC for the concn.-time plot were not significantly different between Japanese and Caucasian subjects (P = 0.64 and P = 0.80, resp.). A single oral dose of aliskiren significantly reduced PRA to a similar extent in Japanese and Caucasian subjects (by 87.5% and 85.7%, resp., compared with baseline; P < 0.01). Aliskiren was well tolerated by both ethnic groups. Conclusions: The oral renin inhibitor aliskiren demonstrated similar pharmacokinetic and pharmacodynamic properties in Japanese and Caucasian subjects. .

Therapeutic potential of renin inhibitors in the management of cardiovascular disorders

Therapeutic potential of renin inhibitors in the management of cardiovascular disorders. Stanton, Alice (Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ire.). American Journal of Cardiovascular Drugs, 3(6), 389-394 (English) 2003 Adis International Ltd. CODEN: AJCDDJ. ISSN: 1175-3277. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. The renin-angiotensin system (RAS) is well recognized for its importance in regulation of BP, electrolyte balance and vascular growth. Pharmacol.Several reagents with their cas registry numbers 11128-99-7 and 173334-57-1 are used here. suppression of the RAS, through ACE inhibition and/or angiotensin receptor blockade, is a proven effective therapeutic approach to the treatment of a range of cardiovascular diseases. Renin is the enzyme that catalyzes the first and rate-limiting step of RAS, the cleavage of angiotensinogen to angiotensin I (A-I). A-I is then further converted by ACE to the biol. active vasoconstrictor, A-II. Interruption of the generation of A-II by renin inhibitors at this highly specific initial step of the cascade would be expected to have similar but not identical effects to those of the already well established RAS antagonists. Due to the lack of effective alternative enzyme pathways, blockade of A-II prodn. may be more effective with renin inhibition than with ACE inhibition, and because of the high specificity of renin for only one substrate, namely angiotensinogen, adverse effects would be expected to be less frequent. It is currently unclear whether blockade of angiotensin II type 1 receptors (AT1), leaving other A-II receptors unblocked, is preferable to the redn. in plasma and tissue A-II levels achieved with either ACE or renin inhibition. The development of early peptidic and peptidomimetic renin inhibitors was hampered by problems with oral bioavailability and high costs of synthesis. However recent work has led to the synthesis of a potent non-peptidic inhibitor of renin, aliskiren, which has acceptable oral bioavailability. This renin inhibitor has been shown to effectively reduce A-II levels in normal volunteers and to lower BP in patients with mild to moderate hypertension. It appears likely that aliskiren is the first of a new class of agents that may prove useful in the management of patients with nephropathy, heart failure and atherosclerosis in addn. to hypertension. .