Early Adequate Mycophenolic Acid Exposure is Associated with Less Rejection in Kidney Transplantation

Pharmacokinetics and Pharmacodynamics of Intensified versus Standard Dosing of Mycophenolate Sodium in Renal Transplant Patients

“…These results support the overall hypothesis that early adequate MPA exposure in renal transplant recipients can be achieved with a higher starting dosage and are consistent with findings from previous studies (4,7,12); however, data from larger studies are needed to confirm whether the pharmacokinetic and pharmacodynamic differences reported here can be translated into improvements in efficacy and safety.…”

“…Whereas the majority of tacrolimus-treated patients achieve adequate MPA exposure early after transplantation (13,14), studies have demonstrated that approximately 50% of patients who are treated with CsA and standard MPA dosages are underexposed (4,7,12,13). Larger initial MMF dosages (up to 4 g/d) have been suggested early after transplantation for achievement of sufficient MPA exposure in combination with CsA (13,15,16).…”

Therapeutic Drug Monitoring of Mycophenolic Acid

“…In the randomized, concentration-controlled trial, MPA trough values also correlated with rejection risk but less significantly (P Ͻ 0.01), presumably as a result of the greater inherent variability of trough concentration values (37). In three retrospective review studies of systematically collected MPA PK data in adult (63,64) or pediatric (38) renal transplant patients who received MMF ϩ CsA ϩ corticosteroids, the early estimated MPA AUC predicted the risk for rejection (Table 2). In two studies that involved adult renal transplant patients who were receiving MMF ϩ CsA ϩ corticosteroids, MPA AUC did not correlate with the rate of acute rejection, but this may have been due to the small number of rejection events recorded in these studies: Five of 46 patients and seven of 42 (65,66).…”

“…A significant association was found for the median value for MPA trough concentration and risk for rejection within the first 30 d after transplantation (68). The FDCC and Opticept prospective therapeutic drug monitoring trials will hopefully provide more comprehensive data on which to base the selection of sampling schedule and best sample The data supporting definition of the upper end of the target therapeutic range are limited for several reasons, including the highly variable timing of plasma sampling in relation to time of adverse effects and the highly variable set of patient factors from study to study causing variable risk for adverse effects (37,64). For renal transplant patients who are on CsA co-therapy, there is no further reduction in acute rejection at AUC values Ͼ60 mg/h per L (37,58); therefore, avoidance of higher exposure would seem prudent on the basis of this information.…”

Clinical Pharmacokinetics of Triple Immunosuppression Scheme in Kidney Transplant (Tacrolimus, Mycophenolate Mofetil and Corticosteroids)

“…Inhibits proliferative responses of T and B-cells to both mitogenic and allospecific stimulation and suppresses antibody formation by B-cells. By preventing glycosylation of lymphocyte and monocyte glycoproteins involved in intracellular adhesion to endothelial cells, MPA may inhibit recruitment of leukocytes to sites of inflammation and graft rejection (Pillans et al, 2001;Kiberd, et al, 2004;van Gelder et al, 1999).…”