Study Of Pharmacokinetics Of L-carnitine Pool In Chinese Aged Volunteers And Treatment Effect Of L-Carnitine And EPO On Uremic Anemia

OBJECTIVE:To repeat HPLC-FL methods to determine the concentration of L-carnitine pool in human plasma.And the HPLC method was used in pharmacokinetic study of L-carnitine pool after single oral administration of L-carnitine oral solution 2g in Chinese aged volunteers。And observe the effect of L-Carnitine and EPO in the treatment of patients with uremic anemia in hemodialysis and the interaction with dosage of EPO.METHODS The plasmas were precipitated by protein precipitation and then precolumn derviatived with 1-AA.The derivatives were analyzed on a Hypersil C₁₈ column,and the mobile phase consisted of acetonitrile-0.1mol·L^-1 ammonium acetate(34:66),the flow rate was 1.0ml·min^-1.The fluorimetric detector set was at 248 nm (excitation wavelength) and 418 nm(emission wavelength).The plasma was collected at Oh,0.5h,1.0h,1.5h,2h,2.5h,3.0h,3.5h,4.0h,5.0h, 6.0h,8.0h,12.0h,24.0h after single oral administration of 2g L-carnitine oral solution in 10 Chinese aged volunteers,The concentrations of L-carnitine pool in plasma were measured by HPLC,Drug Concentration-Time Curves were draw,the pharmacokinetics parameters were calculated by DAS 2.0 software.43 Patients with anemia of uraemia in hemodialysis were randomly divided into 2 groups.L-Carnitine took orally with EPO given simultaneously in therapy group,and the control group given EPO only.All the patients were observed for 12 weeks.The initial dose of EPO in either of two groups was 150 U/kg weekly.The dosage reduced by degrees to maintenance dose when Hb≥100g/L,Hct≥30%.observed the changes of Hb, Hct,EPO dosage before therapy and after therapy and estimate the effect of drug combination on uremic anemia.RESULT:The good linearity were observed over the concentration ranges investigated,2～500μmol·L^-1(LC),0.5～50μmol·L^-1(ALC),0.1～20μmol·L^-1(PLC) in plasma by HPLC.The precision,recoveries stability test of LC,ALC and PLC correspond the requirement in plasma.The methods were proved to be stable,accurate to study the concentrations of L-carnitine in clinical plasma.After oral administration of 2g L-carnitine oral solution,the main pharmacokinetic parameter of LC Cmax is(81.26±20.79)μmol·L^-1,t_1/2β is(63.80±17.25)h,AUC_(0-t) is (1648.32±402.45)μmol·L^-1·h,Tmax is(3.8±0.85)h.ALC:t_1/2α:(6.87±5.74)h,t_1/2β: (38.52±27.21)h,AUC_(0-t):135.65±70.16μmol·L^-1·h,AUC_(0-∞):180.19±68.33μmol·L^-1·h, Tmax:(2.7±0.70)h,Cmax:(12.33±4.67)μmol·L^-1,and PLC:t_1/2α:(3.74±3.62)h,t_1/2β: (28.20±29.75)h,AUC_(0-t):(61.48±49.60)μmol·L^-1·h,AUC_(0-∞): (168.91±384.27)μmol·L^-1·h,Tmax:(3.9±0.86)h,Cmax:(4.85±2.94)μmol·L^-1。In the study of drug combination on uremic anemia,both levels of Hb and Hct were improved(0＜0.05),but it was significantly higher in therapy group(P＜0.05),and the maintenance dose in therapy group was 1 ess than that in contral group.CONCLUSION:The HPLC-FL method was successfully used in pharmacokinetic study of L-carnitine pool after single oral administration of L-carnifine oral solution in Chinese aged volunteers.In addition,L-Carnitine could significantly improve the effect of EPO in the treatment of the patients with anemia of uraemia and reduce the dosage of EPO.