| Objective: Using liquid chromatography-tandem mass spectrometry to detectionconcentration of drug in plasma in order to investigate the rationality of usingL-carnitine injection as adjuvant treatment for chronic heart failure patients.Methods: From August2010to April2012,261chronic heart failure patients in13sitesenrolled this study. All of the subjects were randomly divided into test group or controlgroup. In test group, there were133subjects, with mean age51.94±16.24years old andmiddle weight62.88±12.25kg; While128subjects in control group with mean age52.44±16.51years old and middle weight63.93±14.02kg. The primary drug treatmentin both two groups were digitalis, uretic, vasodilator, ACEI, β-receptor blocker,bosentan, sildenafil, vardenafil and so on. Test group were given L-carnitine injection15ml (l-carnitine3g) per time, IV, Bid for consecutive seven days; while control weregiven L-carnitine placebo injection15ml per time, IV, Bid for consecutive seven days.Blood sample would be collected before and after study for each patient, and usingHPLC tandem MS to detection concentration of free L-carnitine and total L-carnitine inplasma. Before and after treatment, in both two groups would evaluation cardiacfunction and ration of plasma acyl-L-carnitine/free L-carnitine. Primary endpoint wasthe change of cardiac function within24hours of7-day treatment complete, and excellent, effective and invalid were used to describe the changes; Secondary endpointwas the change ration of plasma acyl-L-carnitine/free L-carnitine; Safety was evaluatedwas by AEs, physical/vital signs and laboratory examination. SAS9.3was used forcount and analysis. All statistical tests use a two-sided test, p-value less than0.05isconsidered there is statistical differences.Result:1. There were no statistical differences between test and control groups inweight, systolic pressure, diastolic pressure, temperature, pulse and respiration ofsubjects (P>0.05).2. Before taken drug (baseline), there were no statistical differencesbetween test and control groups of free L-carnitine concentration in plasma. After7-daytreatment, the concentration of free L-carnitine in test group increased23.82±33.23μg/ml in test group compared with baseline, while control group onlyincreased3.66±18.42μg/ml. There had statistical differences between two groups(P<0.001).3. Before taken drug (baseline), there were no statistical differences betweentest and control groups of total L-carnitine concentration in plasma, the concentration oftotal L-carnitine in test group increased37.03±53.17μg/ml in test group compared withbaseline, while control group increased5.26±21.73μg/ml. There had statisticaldifferences between two groups (P<0.001).4. Before taken drug (baseline), there wasno statistical difference between test and control groups of ration of plasmaacyl-L-carnitine/free L-carnitine (P>0.05). After7-day treatment, the ration in test groupwas lower than baseline while in control group was higher, there were no statisticaldifferences in both two group; Also there was no statistical difference between test andcontrol groups of ratio (-0.01VS0.21)(P=0.479).5. Before taken drug (baseline), therewas no statistical difference between test and control groups of cardiac function(P>0.05). After7-day treatment, there was statistical difference between test and controlgroups of cardiac function (P=0.0026). In test group,6subjects were excellent changed,72subjects were effective changed, with total effective rate was60.47%(78/129); While in control group,3subjects were excellent changed,48subjects were effectivechanged, with total effective rate was44.74%(51/114). The difference of total effectiverate in two groups was15.73(3.30%~28.16%), the difference had statisticallysignificant (P=0.0144).6. Before and after treatment, there were no statisticaldifferences between test and control groups in physical/vital signs and laboratoryexamination.Conclusion:1. Set up the method using liquid chromatography-tandem massspectrometry (LC-MS/MS) to detective free l-carnitine and total l-carnitine in plasma,and the endogenous substances in plasma would not interfere determination of samples.2. Patients with chronic heart failure using exogenous L-catnitine based on primary drugtreatment, would increase the content of free l-carnitine in plasma, improve L-carnitinelevel in myocardial cell, improve myocardial energy metabolism, and effectivelyimprove the cardiac function of patients.3. It showed that given L-carnitine injection3g/time, Bid to chronic heart failure patients was safe, effective, and well tolerated. Ithas application prospects in clinic. |
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