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Mycophenolic acid (MPA) plays critical role in maintaining the function of renal allograft. Optimal mycophenolic acid exposure is crucial for its efficacy and good clinical response. Pharmacokinetic of MPA is complex and may be variable in renal transplant recipients. This study aimed to determine the plasma concentrations of mycophenolic acid (MPA) patients treated with mycophenolic mofetil (MMF) and its association with graft function in renal transplant recipients in early post-transplant period.
A total of 11 were enrolled in the hospital-based analytical study. Blood samples for determination of plasma MPA were collected at post-transplant 7th day. Plasma concentrations of mycophenolic acid at time points immediately before drug administration, 0.5 hours, and 2 hours post dose (C0, C0.5, and C2) were determined by validated HPLC-UV method and then, MPA exposures (AUC0-12) were estimated by validated Limited Sampling Strategy. The estimated MPA AUC0-12hr was calculated by using the validated limited sampling strategy equation from the three plasma concentration time points measured. The validated limited sampling strategy equations were used separately for AUC0-12hr of MMF (7.75 + 6.49 × C0 + 0.76 × C0.5 + 2.43 × C2). Clinical responses were assessed by serum creatinine, estimated glomerular filtration rate (eGFR), and total white cells count (WBC), hemoglobin, platelets, and liver function test.
The mean plasma trough concentration was 1.56 ± 1.02 µg/mL; the mean MPA exposure was (AUC0-12) 33.78 ± 20.61 µg.hr/mL. Both mean trough concentration (C0) and mean AUC0-12hr were found to be within the currently recommended therapeutic window of (1-3.5 µg/mL) and (30-60 µg.h/mL). Among the total 11 recipients, MPA exposures were low in 7 recipients (<30 µg.h/mL), optimal in 2 recipients (30 – 60 µg.hr/mL) and high in 2 recipients (>60 µg.hr/mL ).
Wide inter-patient variability of MPA exposures was found in recipients taking MMF with the wide range of 16.61 – 72.77 µg.hr/mL and higher coefficient of variation of 66.01% at post-transplant 7th day.
Regarding the association between MPA exposure of MMF and clinical responses at post-transplant 7th day, there were low positive correlation between AUC0-12hr and creatinine (r = 0.43), low negative correlation between AUC0-12hr and eGFR (r = -0.38) and low negative correlation between AUC0-12hr and liver enzyme, AST.
Association of MPA plasma concentrations of MMF with clinical responses
Wide inter-patient variability, statistically significant difference of MPA exposure between age groups and low correlation between MPA exposures and clinical responses at post-transplant 7th day suggest the need for therapeutic drug monitoring of MPA in Myanmar renal transplant recipients.