Clinical Pharmacokinetics Of Levosimendan Injection

LevosimendanIs a new generation of cardiac drugs,a calcium sensitizer,both the role of calcium ions increase sensitivity(mainly),phosphodiesterase inhibition and vasodilator effect of three.It is different with the common clinical cardiac glycosides,beta receptor agonists and inhibitors of phosphodiesterase three cardiotonic drugs in levosimendan and not by increasing the intracellular calcium concentration to increase myocardial contractility,so there is no risk(such as calcium overload induced arrhythmias,myocardial ischemia or sudden death,further lead to heart failure etc.).A large number of clinical studies have shown that levosimendan can not only improve symptoms and hemodynamics in patients with heart failure,but also prolong the survival time.Levosimendan metabolites in vivo into ring or N-acetyl cysteinyl glycine and cysteine,in vivo metabolism will be completely,through the urine and feces of trace products.The half-life of levosimendan was 1H,and the clearance rate was 3.0mL/(min·kg),of which 54% of the drug was excreted from the urine,and the drug discharged from the feces was about 44%,and more than 95% of the drugs were removed in one week.Levosimendan used in healthy human body,because of different doses may present different degrees of adverse reactions,such as palpitations,blood pressure reduction,nausea,vomiting,headache,etc.,generally do not need special treatment can alleviate.According to the structure,metabolism and the expected concentration range of levosimendan,a HPLC/ESI/MS/MS method was established for the determination of levosimendan in plasma.Agilent 1200 liquid chromatography(Agilent)was used,and the chromatographic column was Agilent Eclipse XDB(150 mm×4.6 mm,i.d.,5 ?m),the mobile phase was methanol,the flow rate was 0.8 mL·min-1,and the temperature of the column was warm.Ion source for electrospray ionization(ESI),ion injection voltage is-4500 V,the temperature is 500?,the source of gas in 1(GS1,N2)gas pressure is 50 psi,2(GS2,N2)for 40 psi pressure,air curtain gas(CUR,N2)pressure is 30 psi;Negative ion mode detection,scanning mode for multiple reaction monitoring(MRM).The linear range of levosimendan was 0.5~1200 ng/mL,and the lower limit of quantification was 0.5 ng/mL.The method is sensitive,specific,stable,accurate and specific.It can be used for the detection of Levosimendan Injection biological samples.Determination of serum concentration of levosimendan with HPLC/MS/MS method.The pharmacokinetic characteristics and safety evaluation test,Levosimendan Injection pharmacokinetics,and provide reference for clinical safe and rational drug use.