Pharmacokinetics of mycophenolic acid in children with clinically stable idiopathic nephrotic syndrome receiving cyclosporine

Abstract

In children with clinically stable INS receiving CyA, C2 monitoring was the most useful single parameter for estimating MPA pharmacokinetics. Younger children required higher MMF doses.

The Evaluation of Multiple Linear Regression–Based Limited Sampling Strategies for Mycophenolic Acid in Children with Nephrotic Syndrome

“…The search of the literature returned 29 studies meeting the requirements concerning MLR LSSs for MPA and fMPA, dated 1998–2020. We applied 48 MPA LSSs [ 8 , 9 , 14 , 21 , 22 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ] and five fMPA LSSs [ 35 , 36 , 42 ] found in the literature to calculate the predicted area under the (0–12 h) time–concentration curve (AUC pred ) in children with nephrotic syndrome treated with MMF, and compared the results with AUC total . In the majority of studies, calcineurin inhibitors (CsA or tacrolimus (Tac)) were co-administered with MMF.…”

“…Two of nine the best LSSs included liver transplant recipients [ 28 , 29 ]. Surprisingly, the LSSs established for children with nephrotic syndrome [ 14 , 25 ] or lupus erythematosus [ 21 ] performed poorly as they did not fulfill the criteria: the values of r 2 were below 0.800, and ≤50% of the AUC pred values were within ±15% of the AUC total . These poor results may be explained by one time point equation in the Hibino et al study [ 14 ] and the relatively high intercept.…”

“…This evidence suggests that the MPA C max and C max2 influence its AUC the most, and the blood samples should be collected at least in three time points near C max and C max2 to precisely predict the AUC. According to the literature, for children with nephrotic syndrome C 2 or time points up to 2 h after MMF administration should be included in the MPA LSS [ 14 , 25 ]. The inclusion of C 6 makes using LSS cumbersome.…”

“…The MMF active moiety, mycophenolic acid (MPA), is characterized by complex and variable pharmacokinetics and high serum albumin binding (97–99%) [ 1 , 5 ]. MPA pharmacokinetics in renal transplant recipients are widely described in the literature [ 1 , 6 , 7 , 8 , 9 , 10 ], however, although the pharmacokinetics are assumed to be different, there are few studies concerning children with nephrotic syndrome treated with MMF [ 11 , 12 , 13 , 14 ]. In our previous study [ 11 ], we observed that the target values of the pharmacokinetic parameters, such as the concentration before the next dose (C 0 ) and the area under the concentration—time curve from 0 to 12 h (AUC total ), in children with nephrotic syndrome treated with MMF should be higher than those recommended after renal transplantation [ 1 ].…”

Mycophenolate mofetil is inferior to tacrolimus in sustaining remission in children with idiopathic steroid-resistant nephrotic syndrome

“…Studies in patients with frequent relapses show that targeting higher levels of 12-hour area under the curve of mycophenolic acid, ranging from 30 to 45 mg$h/ml, were associated with sustained remission and lower corticosteroid requirement. [46][47][48][49] Similarly, an area under the curve >60 mg$h/ml and a trough concentration >3 mg/ml were associated with remission of proteinuria in children with nephrotic syndrome or lupus nephritis. 50 However, the dose of MMF in the current study was comparable to those reported previously (i.e., 25-35 mg/kg or 800-1200 mg/m 2 20,26,29 including studies that demonstrate pharmacokinetic adequacy.…”