To obtain an adequate immunosuppressive effect of mycophenolate mofetil (MMF), various equations have been used for estimating the area under the concentration curve (AUC) for mycophenolic acid (MPA) under a limited sampling strategy. Most of them, however, involved cyclosporine (CYA) -based immunosuppression. In this study, we measured chronological blood concentrations of MPA when included in tacrolimus (TAC, alternative calcineurin inhibitor) -based triple-drug immunosuppression in renal transplant recipients and investigated the effectiveness of a limited sampling strategy which minimized patients' inconvenience.
Measurement of MPA concentrations in consecutive samplings over a 24-hour period in 6 renal transplant recipients receiving TAC-based triple-drug immunosuppression therapy (MMF dose : 1250-2000 mg/day, twice a day), showed substantial inter-patient and intra-patient variability in MPA pharmacokinetics. The second MPA peak was observed in 8 concentration profiles. There were no significant differences in T
max, T
lag, dose-normalized C
max, pre-dose concentration (C
0), and AUC (0-12) (AUC (τ)) between morning and evening dosing.
Regarding a relationship between AUC (τ) and the MPA concentrations for each sampling point, despite the substantial variation in MPA pharmacokinetics, a significant correlation was found between C
0 and AUC (τ) (r
2= 0.734). The highest r
2 value was obtained at C
8 (r
2=0.852). The optimum combination of sampling time points for estimating AUC for MPA using stepwise linear regression was C
0, C
3, C
8 (r
2= 0.964) and this combination had the lowest maximum prediction error (22.6%) in the estimation of AUC (τ). From the above findings, we recommend the use of the formula AUC (τ) (μg·h/ mL) = 7.82 +3.58· C
0 + 1.87· C
3 + 7.15 ·C
8 for estimating the AUC for MPA in renal transplant recipients also receiving TAC.
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