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

  title={Pharmacokinetics, Pharmacodynamics and Safety of a Single Dose of Imarikiren, a Novel Renin Inhibitor, in Healthy Male Subjects},
  author={Kumi Matsuno and S. Kuroda and Shingo Tanaka and Hiroyuki Nakamichi and Tomoya Kagawa and Emiko Koumura},
  journal={Basic \& Clinical Pharmacology \& Toxicology},
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… Expand
Pharmacokinetics and Safety After a Single Dose of Imarikiren in Subjects with Renal or Hepatic Impairment
RI and HI are associated with limited changes in imarikiren pharmacokinetics and Imarikirens was safe and well-tolerated, regardless of the severity of RI or HI. Expand
Efficacy and Safety of Imarikiren in Patients with Type 2 Diabetes and Microalbuminuria: A Randomized, Controlled Trial.
Imarikiren resulted in a dose-dependent improvement in albuminuria compared with placebo, and it was well tolerated in patients with type 2 diabetes mellitus and microalbuminuria. Expand
Development of a novel murine heart failure model overexpressing human renin and angiotensinogen
The results suggest that this newly generated triple‐tg heart failure model is useful to evaluate the cardioprotective effects of human renin inhibitors at clinically relevant doses, thereby minimizing the concerns of off‐target effects related to much higher drug exposure than that achieved in clinical study. Expand


Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in Japanese and Caucasian subjects.
The oral renin inhibitor aliskiren demonstrated similar pharmacokinetic and pharmacodynamic properties in Japanese and Caucasian subjects. Expand
A Randomized, Single‐Center, Double‐Blind, Placebo‐Controlled Multiple‐Dose Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Imarikiren in Healthy Adult Nonelderly and Elderly Male Subjects
Assessment of the safety and pharmacokinetics/pharmacodynamics of multiple oral administrations of imarikiren in healthy nonelderly and elderly Japanese male subjects found it safe and well tolerated with no drug accumulation and strong and sustained suppression of plasma renin activity. Expand
Oral direct renin inhibition: premise, promise, and potential limitations of a new antihypertensive drug.
The premise, promise, and potential limitations of this new class of renin-angiotensin system inhibitor, aliskiren, recently received approval for the treatment of hypertension are addressed. Expand
Discovery of TAK-272: A Novel, Potent, and Orally Active Renin Inhibitor
The aspartic proteinase renin is an attractive target for the treatment of hypertension and cardiovascular/renal disease such as chronic kidney disease and heart failure. We introduced an S1′ siteExpand
The past, present and future of renin-angiotensin aldosterone system inhibition.
The history of RAAS inhibition is presented including a summary of key heart failure, myocardial infarction, hypertension and atrial fibrillation trials, and recent developments are discussed including implementation and optimization of current drug therapies. Expand
Oral direct renin inhibition: premise, promise, and potential limitations of a new class of antihypertensive drug
  • Am J Med
  • 2008
Committee for Medicinal Products for Human Use. Guideline on the investigation of bioequivalence