Pharmacokinetic and Tissue Distribution of the Innovative Calcium Sensitizer-M6 Using an High Performance Liquid Chromatography-Ultraviolet Test Method in Rats

Piperphentonamine hydrochloride (PPTA) is a new calcium sensitizer that increases cardiotonic function by enhancing the sensitivity of myocardial contraction protein to Ca2+ instead of increasing the concentration of Ca2+ in myocardial cells. M6, the active metabolite of PPTA, has improved drug properties that could allow its use in the clinic. In this study, a pharmacokinetic study of M6 showed that its pharmacokinetics parameters, such as T 1/2 and MRT, were approximately 50 times higher than those of pro-drug PPTA. The tissue distribution study also implied that M6 can penetrate the blood-brain barrier. Data from a plasma protein binding analysis showed that M6 binds strongly to plasma proteins and in particular suggest that it is highly stable in human plasma. Use of an oxygen-glucose deprivation cell model demonstrated that M6 can relieve the damage caused by oxygen-glucose deprivation in PC-12 cells, neurons, and cardiomyocytes. Our results demonstrate that we have established a fast, convenient, and effective HPLC method to analyze M6 levels that allows for studies of its pharmacokinetics and tissue distribution in the rat, the data from which suggest that it has potential utility in the clinic.