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Estimation of Abbreviated Mycophenolic Acid Area Under the Concentration- Time Curve during Stable Post-transplant Period by Limited Sampling Strategy

[ Vol. 15 , Issue. ]

Author(s):

Asieh Karimani, Hasan Abedi, Fatemeh Nazemian, Atena Poortaji and Amir Hooshang Mohammad pour* Pages 1-8 (8)

Abstract:


Background: The area under the concentration-time curve (AUC) of mycophenolic acid (MPA), is a valid prognosticator of the risk of rejection and the gold standard in its therapeutic drug monitoring (TDM), over time posttransplantation.

Objective: This study aimed to investigate MPA pharmacokinetic parameters, as well as developing a limited sampling strategy (LSS) to estimate an abbreviated MPA AUC, in the stable phase post-renal transplantation.

Methods: In this study 19 patients with normal graft function (glomerular filtration rate >70 ml/min) who fulfilled inclusion & exclusion criteria were involved. Blood samples at various times were taken in the stable phase after transplantation. MPA plasma concentration was measured by reverse-phase high-performance liquid chromatography. MPA AUC0–12h was calculated using the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal time points of MPA levels that could be used to yield model equations best fitted to MPA AUC 0- 12h. The findings of this study were compared with the results of our previous study, which was done similarly in the early phase post-renal transplantation.

Results: The results demonstrated that the MPA-AUC and clearance were not affected over time, but MPA-tmax was significantly lower in the stable phase in comparison with the early phase (P=0.001). The best regression equation for AUC estimation in the stable phase was AUC=9.57*C6+27.238 (r2=0.907). The validation of the method was performed using the jackknife method. The mean prediction error of these models was not different from zero (P > 0.05) and had a high root mean square prediction error (7.91).

Conclusion: In conclusion, the pharmacokinetics of MPA could be affected by time after transplantation, make it essential to develop a limited sampling strategy granted an efficacious approach for therapeutic drug monitoring during the stable post-transplant period.

Keywords:

Kidney transplantation, mycophenolic acid, pharmacokinetics, renal, time, area under curve

Affiliation:

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Nephrology Section, Department of Internal Medicine, Imam-Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad



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