Determination Of MPA,MPAG In Human Plasma & Correlation Study Between Their Pharmacokinetic Parameters And Clinical Events In Chinese Renal Transplant Patients Treated With Oral MMF

Purposes (1)To develop a HPLC method for the determination of MPA, MPAG concentration in human plasma;(2)To study the pharmacokinetics of MPA, MPAG after single and multiple oral administration of MMF;(3)To study the relationship between pharmacokinetic parameters and clinical events.Methods (1)Compare and choose the best conditions of sample preparation and chromatography separation;(2)12 renal recipients were included in the pharmacokinetic study ofMPA, MPAG. Blood sample were obtained at 0, 0.5, 1, 1.5, 2 , 2.5, 4, 6, 8,10,12h after MMF oral administration, 2 days before grafting and 12 daysafter grafting. Determine the plasma concentration of MPA, MPAG and makethe concentration-time curve. Use DAS (Drug And Statistics) program to choose the pharmacokinetic model and calculate the pharmacokinetic parameters.(3)22 renal recipients were included in the correlation analysis study. Blood sample were gathered from all the recipients at 4th, 12th, 21st, 30th, 45th, 60th , 90th days after grafting. Data about clinical events (side effects oracute rejection) were collected simultaneously. Use SPSS statistic program to study the relationship between pharmacokinetic parameters and clinical events.Results ?The determination method is: the plasma sample was de-protein with CH3CN, then separation was achieved on the BDS Hypersil Ci8(250mm X 4.6 mm, 5 u m) column. Gradient elution was adopted and the flow rate was 1.0 mL-min*1. The samples were measured at UV 254nm. The calibration curves of MPA and MPAG were linear over the range of 0.5 ~ 40mg-L"'(r=0..9999) and 1—200 mg-L'1(r=0..9999) respectively .The limit ofdetection were O.Smg-L"1 and lmg-L'1. The methodology recoveries were 98.33%~100.4% and 99.95%~101.1%. The inter-day RSD were 1.0-1.5% and 0.6-3.0%, the within-day RSD were 1.0-4.4% and 2.6-4.8%. The assay was simple, rapid, and sensitive. It is satisfactory to be used on study of the pharmacokinetics and monitor the concentration of MPA and MPAG in renal transplantation patients.?Studied the pharmacokinetics of MPA, MPAG after single andmultiple oral administration of the pro-drug MMF in Chinese patients with renal transplantation. The MPA plasma concentration-time profiles were fitted as a two compartment open model and the MPAG plasma concentration-time profiles were fitted as a single compartment open model with a linear kinetic absorption. Compared the results with literature reports in other countries and saw some difference. But whether the race difference would influence pharmacokinetic parameters of MPA and MPAG or not, it still needs further research to confirm.?The correlation analysis discovered MPA-Co has strong correlation with side effects and AR (acute rejection). The discrimination threshold for side effects was 1.08mg/L with sensitivity of 62.8% and specificity of 78.4%.and specificity of 83.3 %. This study suggests that MPA-Co might be an appropriate pharmacokinetic monitoring parameter for renal transplantation.