Therapeutic Drug Monitoring Of Myfortic In Chinese Renal Allograft Recipients

Myfortic is an immunosuppressant which is widely used after solid organ transplantation in clinic.Myfortic has a narrow therapeutic window.There is great individual difference in Myfortic pharmacokinetic,which can be affected by different pathophysiological factor.In this study,the pharmacokinetic of Myfortic in Chinese renal allograft recipients was studied,which can provide useful information for the rational usage of Myfortic.Part 1.The objective of this study is to observe the pharmacokinetics of Myfortic and establish a model equation by less-sampling strategy?LSS?for abbreviated MPA AUC calculation in Chinese renal allograft recipients.There are 30 renal-transplant recipients in the study,who were treated with Myfortic?1.44g/d?in combination with cyclosporine?CsA?and prednisone?Pred?.Plasma MPA concentration were determined2 weeks post-transplant by EMIT method at pre-medication,0.5,1,1.5,2,4,6,8,10 and12 hour after oral Myfortic administration.The MPA AUC_0-12h-12h were calculated using the trapezoidal rule and the abbreviated MPA AUC model equation fitted to 30 MPA AUC_0-12h profiles was generated by multiple regression analysis.The pharmacokinetics of Myfortic in 30 renal-transplant recipients manifested great inter-patient difference.The mean MPA AUC0-12h was?47.64±25.14?mg·h/L.The abbreviated MPA AUC model equation:AUC=27.14+0.87×C_1.5+0.88×C₂?r²=0.67?,or AUC=3.98+2.03×C₂+2.18×C₄+1.91×C₆+5.08×C₈?r²=0.79?,resulting in better correlation between estimated AUC and full profile AUC_0-12h;the absolute prediction error was?28.8±24.8?%and?12.8±10.1?respectively.In 30 recipients,the difference between MPA AUC and full MPA AUC_0-12h was within±15%.MPA pharmacokinetics in Chinese renal allograft recipients manifests a substantial inter-individual variability.Two sample model equations best fitted to Full MPA AUC_0-12h were recommended for MPA therapeutic drug monitoring?MPA TDM?in renal allograft recipients.We collected more data of MPA TDM and clinical outcomes in patients who underwent renal allograft transplantation,and then we established the population pharmacokinetics?PKK?model of Myfortic 554 MPA concentration data,from 53 renal allograft racipients collected retrospectively and full-time concentration in 30 patients were analyzed.Pharmacokinetics of Myfortic was best described by a one-compartment disposition model followed by a first-order absorption process.The PPK model developed in this study could quantitatively investigate the effects of different factors on the pharmacokinetics of Myfortic and can be used for optimizing Myfortic dose in Chinese renal-transplant recipients.