Therapeutic Drug Monitoring of Mycophenolic Acid in Lupus Nephritis

Abstract

In recent years, mycophenolate mofetil (MMF)-based immunosuppressive regimen was recommended in induction and in maintenance therapy in lupus nephritis (LN), one of the most severe and common manifestations of systemic lupus erythematosus. However, no recommendations were made so far regarding monitoring of mycophenolic acid (MPA) plasma concentrations. Therapeutic drug monitoring (TDM) constitutes a practical tool to ensure optimal posology. In renal transplantation, it was proved that acute allograft rejection incidences decreased when the recommended MPA target exposure has been maintained (30-60 mg·h·L). The results obtained in the field of transplant medicine indicate the potential benefit of carrying out TDM in LN. To date, the correlation of MPA exposure and clinical outcomes in the population of LN patients was the objective of just a few studies. The aim of this review was therefore to present TDM studies in LN patients on MMF therapy and to compare their results. Based on the conclusions drawn from TDM studies in LN, it can be suggested that the area under the concentration-time curve threshold values of 30-45 mg·h·L can potentially be associated with favorable treatment outcome. Moreover, the majority of the analyzed studies indicate relatively good correlation between trough concentration and the area under the concentration-time curve in patients treated with MMF that constitutes an important implication for TDM approach in routine setting. The threshold of 3 mg/L can potentially be recommended as a target trough value.

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

“…It has been concluded based on literature review that total MPA predose concentration value of 3 μg/mL may be associated with a higher probability of LN remission [1,5]. In our study, only 32.1% of samples reached the recommended value; however, it should be beared in mind that standard MMF fixed-dosing protocol was administered in both clinical centers.…”

“…The mean maximum concentration in case of both total and free MPA was observed 0.5 h after MMF intake. An important result was that only 9 out of 28 samples (32.1%) for total MPA predose concentration exceeded the border value of 3 μg/mL recommended in the literature for LN treatment [5,19]. No statistically significant differences for MPA free fraction between three time points (p = 0.7547) were observed.…”

“…Monitoring of MPA plasma concentrations in transplant patients resulted in the reduction of the acute graft rejection episodes occurrence [3,4]. To date, there are no recommendations regarding therapeutic drug monitoring (TDM) in LN [1,5] although it was demonstrated that MPA exposure correlates with the treatment outcome [6,7]. This suggests that dose adjustment to the MPA target concentrations range in the LN patients may be more beneficial than standard fixed dosing protocol.…”

“…This suggests that dose adjustment to the MPA target concentrations range in the LN patients may be more beneficial than standard fixed dosing protocol. However, it still needs to be evaluated as limited number of studies have been published so far [5].…”

Free mycophenolic acid determination in human plasma ultrafiltrate by a validated liquid chromatography–tandem mass spectrometry method

“…Although the general routine monitoring of MPA is not currently mandatory, there is a worldwide recognized need for TDM of MPA that is attracting growing clinical interest particularly for specific patient populations that may benefit from the TDM approach (Dasgupta, ; Kelly & Butch, ; Kuypers et al . , ; Łuszczyńska & Pawiński, ; Seger et al . , ).…”