Pharmacokinetics, Pharmacodynamics and Safety of a Single Dose of Imarikiren, a Novel Renin Inhibitor, in Healthy Male Subjects

Basic & Clinical Pharmacology & Toxicology
Kumi MatsunoEmiko Koumura

Abstract

Imarikiren hydrochloride (TAK-272/SCO-272) is a novel direct renin inhibitor with potential indications for cardiovascular and renal diseases. This phase I study evaluated the pharmacokinetics, pharmacodynamics and safety of a single oral administration of imarikiren in healthy Japanese male subjects. The Dose-Ascending part (double-blind, placebo-controlled, parallel-group design; n = 60) comprised six steps from 5 to 200 mg (n = 8 for imarikiren and n = 2 for placebo per step). The Food Effect part (n = 12) was an open-label, 2 × 2 crossover design with a dose of 50 mg to evaluate the effect of food on the pharmacokinetics and safety of imarikiren. There was a generally linear relationship between dose and area under the plasma concentration-time curve (0 to infinity) or maximum plasma concentration of imarikiren. Food had no clinically significant effect on the exposure of imarikiren. Inhibition of plasma renin activity was rapid and lasted up to 24 hr at all doses. Plasma active renin concentration increased, reaching a maximum at approximately 6 hr, in a nearly dose-dependent manner. Across both study parts, the number of subjects with treatment-emergent adverse events ranged from 0 to 3 per group with no dependency on dos...Continue Reading

References

Apr 1, 2008·The American Journal of Medicine·Moiz M ShafiqRonald G Victor
Nov 6, 2012·International Journal of Cardiology·Robert J MentzBertram Pitt
Oct 25, 2016·ACS Medicinal Chemistry Letters·Yasuhiro ImaedaTakanobu Kuroita

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Citations

Feb 14, 2019·Clinical Journal of the American Society of Nephrology : CJASN·Sadayoshi ItoYuusuke Umeda

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