Safety, Tolerability, and Pharmacokinetics of NK-104-NP

International Heart Journal
Kaku NakanoKensuke Egashira

Abstract

Pulmonary hypertension (PH) is a disease with poor prognosis, caused by the obstruction/stenosis of small pulmonary arteries. Statin is known to have vasodilating and anti-inflammatory property and is considered to be a candidate of therapeutic agents for the treatment of PH, but its efficacy has not been verified in clinical trials. We have formulated pitavastatin incorporating nanoparticles composed of poly (lactic-co-glycolic acid) (NK-104-NP) to improve drug delivery to the pulmonary arteries and evaluated their safety and pharmacokinetics in healthy volunteers. To accomplish this purpose, phase I clinical trials were conducted. In the single intravenous administration regimen, 40 healthy subjects were enrolled and PK (pharmacokinetic) parameters in 4 groups (1, 2, 4, and 8 mg as pitavastatin calcium) were as follows: 1.00 hour after the administration, the plasma concentration of pitavastatin reached Cmax (the maximum drug concentration) in all groups. Cmax, AUC0-t (area under the curve from time 0 to the last measurable concentration) and AUC0-∞ (area under the curve from time 0 extrapolated to infinite time) were increased in a dose-dependent manner. Population pharmacokinetic analysis based on these results indicated no...Continue Reading

References

Feb 1, 1983·Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology·T SugitaJ T Reeves
Aug 1, 1997·Journal of the American College of Cardiology·S M ShapiroB H Brundage
Nov 10, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·M Takemoto, J K Liao
Sep 3, 2002·Journal of the American College of Cardiology·Olivier SitbonGérald Simonneau
Oct 18, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Yasuhiro IkedaKatsuo Sueishi
Jun 15, 2004·Journal of the American College of Cardiology·Giuseppe G PietraR M Tuder
Feb 6, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Reda E GirgisPaul M Hassoun
Jul 9, 2009·Journal of the American College of Cardiology·Rubin M TuderSheila G Haworth
Aug 29, 2009·The AAPS Journal·Radojka M Savic, Mats O Karlsson
Mar 1, 2012·The European Respiratory Journal·Wei-Jie ZengUNKNOWN Atorvastatin in Pulmonary Arterial Hypertension (APATH) Study Group
Aug 11, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Ryoji NagahamaKensuke Egashira
Sep 8, 2012·American Journal of Respiratory and Critical Care Medicine·Rajkumar SavaiRalph T Schermuly
Jul 5, 2013·American Journal of Respiratory and Critical Care Medicine·James R KlingerMark T Gladwin
Oct 4, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mathew J WongRobert P Jankov

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Citations

Apr 17, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Rahul MittalAdrien A Eshraghi
Nov 28, 2019·International Journal of Molecular Sciences·Kazufumi NakamuraHiroshi Ito
Jul 23, 2020·Advanced Drug Delivery Reviews·Romain BrusiniPatrick Couvreur
Jan 1, 2020·Journal of Vascular Surgery. Vascular Science·Yutaka MatsubaraAlan Dardik
Apr 29, 2021·Journal of Atherosclerosis and Thrombosis·Takuya MatsumotoKensuke Egashira
Sep 4, 2020·ACS Chemical Neuroscience·Hye Jee HahnAnjan Debnath
Sep 4, 2021·CNS & Neurological Disorders Drug Targets·Rishabh VermaMohamad Taleuzzaman

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