IMPAIRED RENAL FUNCTION, NOT ETHNICITY, ALTERS MYCOPHENOLIC ACID PHARMACOKINETICS IN AFRICAN-AMERICAN RENAL TRANSPLANT PATIENTS

Abstract

323 Important to designing optimal mycophenolate mofetil(MMF) dosing in individual renal transplant patients(RTP) is knowing if there are significant effects of ethnicity on mycophenolic acid(MPA) pharmacokinetics(PK). Thus we evaluated the following in 20 caucasian(Cau) and 13 African-American(AA) RTP: 2hr MPA AUC which correlates well to the 12 hr AUC (HaleM, Cost B1 Medicine 1997, pp229-35), MPA free fraction (MPAff), free MPA AUC2(fMPA AUC2) and pre-dose concentrations of MPA glucuronide (MPAGpre). Methods: On the day of transplant surgery each RTP received MMF(1 g BID), CsA(HPLC target blood concentration range: 100-250 μg/L) and steroids. In all RTP, MPA AUC2 (validated HPLC) were determined on post-surgery days 4,7,14,28 and 90 in the AM after an overnight fast. Results: PK parameters in all AA vs Cau RTP were not significantly different (Transplantation 1998; 66:S5); there was a trend to lower MPA AUC2 values in the AA RTP. But, when the 8 AA RTP with delayed graft function(DGF) were compared to nonDGF RTP, there were significant differences between AA DGF vs all nonDGF RTP(5AA, 17Cau) in the early post-surgery period. Lower MPA AUC values in DGF AA RTP, days 4-14, are offset by the increased MPAff such that fMPA values are comparable between the 2 groups except on day 7. Significantly higher fMPA AUC2 in DGF AA RTP, day 7, shows that early post-surgery there is an increase in pharmacologically active fMPA concentration. All PK values were comparable in DGF and nonDGF RTP by day 28. The 5 nonDGF AA RTP had PK values comparable to those of Cau nonDGF and the 3 Cau DGF had PK parameters comparable to those of AA DGF (data not shown). (Table)TableConclusions: DGF AA RTP have altered MPA PK early post-surgery. The temporary provision of increased active fMPA concentration affords additional immunosupression in DGF RTP. By day 28 all PK parameters in the AA DGF patients were comparable to the values in nonDGF RTP. These data are consistent with the hypothesis that DGF, not ethnicity, causes a change in MPA PK early post-transplant and that for RTP with impaired renal function both fMPA AUC2 and MPA AUC2 may be needed to evaluate MPA exposure.