Pharmacokinetic And Clinical Effects Studies Of Mycophenolate Mofetil In Lupus Nephropathy Patients

Objective:To establish HPLC determination method of Mycophenolate Mofetil(MMF)blood drug concentration,to explore pharmacokinetic of MMF in LN patients,to monitor steady valley blood concentrations of MMF in patients with LN,to investigate the clinical curative effect of oral MMF,the changes of related clinical indicators and the adverse reactions,to explore the relationship between steady blood medicine valley concentration and efficacy and to identify the LN patients starting doses of oral MMF and effective blood concentration of medicine valley.Methods:High performance liquid chromatography(HPLC)method was developed for the determination of MMF blood drug concentration.Pharmacokinetic model was established and pharmacokinetic parameters were calculated.Limited blood collection point method was used to predict AUC of MPA.The patients were divided into the effective and ineffective group according to the stable valley concentration and its clinical effects.The effective valley concentrations of MMF in lupus nephropathy patients were identified by means of ROC curve.The blood drug concentration was calculated to determine the best initial clinical dose.Results;1.There is a good linear relationship in the range of 1.25-50 mg/L(r =0.9999,n = 5).The lowest detection limit is 0.5 mg/L.The method recovery was 101.03%while RSD was 4.60%on average.The extraction recovery of MPA was 88.71%while RSD was 4.20%.Internal standard extraction recovery rate was 79.35%while RSD was 2.40%.The inter-day differenc of MPA was 5.20%,while within-day difference of MPA was 6.10%.2.After the first oral administration of MMF,the equation:AUC0-12=11.464+1.472C1+2.539C4+7.171C8(r=0.979)could be found,according three point fitting of C1?C9 and C8,while AUC0-12,2=7.381+1.281C1+1.866C4+2.985C6+6.178C8(r=0.993)were found,according to the four point fitting of C1?C4?C6 and C8.3.The steady state valley concentrations of MAP of effective group are significantly higher than that of ineffective group.The threshold of the effective valley concentrations of MMF is 4 mg/L.According to blood concentration,the optimum initial clinical dose is 0.75 g,twice a day.Conclusions:1?The HPLC method is is simple,accurate and fast,sensitive and reproducible,which could meet clinical requirement.It coule be used to monitor MPA blood concentration.2.There are relatively more individual differences and it's necessary to monitor MPA blood concentration.After the first oral administration of MMF,the equation:AUC0-12=11.464+1.472C,+2.539C4+7.171C8(r=0.979)could be found,according three point fitting of C1?C4 and C8,while AUC0-12=7.381+1.281C1+1.866C4+2.985C6+6.178C8(r=0.993)were found,according to the four point fitting of C1?C4?C6 and C8.3.The threshold of the effective valley concentrations of MMF is 4 mg/L after 3-month therapeutic time.The optimum initial clinical dose is 0.75 g,twice a day.