Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

Abstract

AIMSThe aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. METHODSSix blood samples were drawn pre-and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C 0 ), maximum concentration (C max ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drugrelated adverse events. [7][8][9][10][11][12][13][14][15][16][17][18][19] was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). RESULTS Dose CONCLUSIONSThis study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis.

Pharmacokinetics of free and total mycophenolic acid in adult lupus nephritis patients—implications for therapeutic drug monitoring

“…Moreover, high between-patient variability in MPAshortened AUC was observed with extremes of 5.69 and 50.05 μg•h/mL•g (CV% of 53.5%) as well as 37.97 and 590.5 ng•h/mL•g (CV% of 63.8%) for dose-normalized total and free MPA AUC 0-2 , respectively. It is in accordance with other pharmacokinetic studies carried out in LN [2,7,20]. Recently, Abd Rahman et al [2] reported CV% of 50% and 53% for dose-normalized total and free MPA AUC 0-12 , Fig.…”

“…According to our knowledge, there have been two studies so far which evaluated not only total but also free MPA pharmacokinetics in adult LN patients [2,11]. However, our report presents research that additionally examined relationship between free and total MPA concentration-related parameters in this particular population of patients.…”

“…Mycophenolate mofetil (MMF), a prodrug of an immunosuppressive agent mycophenolic acid (MPA), is recommended by the Joint European League Against Rheumatism (EULAR) and European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) for the management of class III and IV lupus nephritis (LN) in induction as well as the maintenance therapy [1]. MPA pharmacokinetics is characterized by the considerable inter-and intrapatient variability thus fixed dose approach in the LN population may not be beneficial for the renal outcome improvement in every patient [2]. Monitoring of MPA plasma concentrations in transplant patients resulted in the reduction of the acute graft rejection episodes occurrence [3,4].…”

“…According to our knowledge, there were only two studies published that explored the effect of both total and free MPA exposure on adult LN patients outcome [2,11]. However, none of them has evaluated the relationship between corresponding free and total MPA pharmacokinetic (PK) parameters and the effect of hypoalbuminemia on MPA plasma protein binding.…”

Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

“…Median as well as mean dose-normalized values of MPA C trough and AUC 0-12 in our study were similar or slightly higher than in adult renal transplant recipients (Engelbertink et al, 2002;Kuypers et al, 2003;Shaw et al, 2004;Tedesco-Silva et al, 2005). On the other hand, median and mean dose-normalized MPA C trough and AUC 0-12 in our study were higher than those obtained in patients with lupus nephritis (Abd Rahman et al, 2015;Alexander et al, 2014).…”