What is the intrapatient variability of mycophenolic acid trough levels?

Abstract

TDM of MPA, the active compound of MMF, is rarely used despite its substantial intra- and interpatient variability. Little is known about the utility of long-term MPA TDM. Data are expressed as mean (one standard deviation). All available data from 27 renal transplant recipients (mean age at transplantation: 7.7 [5.0] yr) with an average follow-up of 9.3 (4.6) yr were analyzed. MPA levels were measured using the EMIT. GFR was measured using cystatin C and eGFR was calculated using the Filler formula. Intrapatient CV of the trough level was calculated as the ratio of the mean divided by one standard deviation. Mean cystatin C eGFR was 56.9 (24.4) mL/min/1.73 m(2) . There was a weak but significant correlation between the MPA trough level and the AUC (Spearman r = 0.6592, p < 0.0001). A total of 1964 MPA trough levels (73 [45]/patient) were measured, as compared to 3462 Tac trough levels (144 [71]/patient). The average MPA trough level was 3.01 (1.26) mg/L and the average trough Tac level was 7.3 (1.8) ng/mL. Intrapatient CV was statistically higher (p = 0.00093) for MPA at 0.68 (0.29) when compared to Tac with a CV of 0.46 (0.12). CV did not correlate with eGFR. Intrapatient MPA trough level CV is significantly higher than for Tac, while CV for both MPA and Tac was high. MPA trough level monitoring may be a feasible monitoring option to improve patient exposure and possibly outcomes.

Pharmacokinetics of Mycophenolic Acid after Intravenous Administration of Mycophenolate Mofetil to Healthy Cats

“…One of the most remarkable aspects of the plasma disposition of MPA in cats is the relatively high interindividual variability of its plasma concentrations. This point does not seem to be feline specific, as it has also been a concern in human patients . The high variability of MPA concentration in plasma can be translated into unpredictable drug responses, which raises a reasonable concern in patients that require sustained suppression of the immune system and are not being co‐treated with other immune suppressants.…”

“…This point does not seem to be feline specific, as it has also been a concern in human patients. 9,21 The high variability of MPA concentration in plasma can be translated into unpredictable drug responses, which raises a reasonable concern in patients that require sustained suppression of the immune system and are not being co-treated with other immune suppressants. In our study, the variability of the analytical method was very low (~10%) and within the conventional standard limits.…”

The development of a population physiologically based pharmacokinetic model for mycophenolic mofetil and mycophenolic acid in humans using data from plasma, saliva, and kidney tissue

“…A limited‐sampling strategy was established for MPA in human plasma where a good correlation between certain sampling time points and the in vivo observed plasma was found (Johnson et al, ; Mathew et al, ; Mohammadpour et al, ; Musuamba et al, ; Todorova et al, ). More work is needed to establish a limited‐sampling strategy for MPA in saliva and for MMF in both saliva and plasma.…”

“…Immunosuppressant therapy requires therapeutic drug monitoring (TDM) to avoid graft rejection resulting from the narrow therapeutic window and high exposure variability (Mohammadpour, Elyasi, Vahdati, Mohammadpour, & Shamsara, 2011;Schiff, Cole, & Cantarovich, 2007). Limited sampling strategy for mycophenolic acid (MPA) in plasma was followed to reduce the burden and cost of therapeutic drug monitoring of mycophenolic acid (Johnson et al, 1999;Mathew et al, 2010;Mohammadpour et al, 2008;Musuamba et al, 2009;Todorova, Huang, Kobrzynski, & Filler, 2015).…”

Pharmacokinetic Variability of Mycophenolic Acid in Pediatric and Adult Patients With Hematopoietic Stem Cell Transplantation

“…Because of the complex pharmacokinetics of MPA, high intra‐ and interpatient pharmacokinetic variability of MPA has been observed in organ transplant patients, childhood‐onset systemic lupus erythematosus patients, and HSCT patients. MPA exposure could vary more than 10‐fold between patients, leading to a significant therapeutic challenge . This study was conducted to gain insights into the pharmacokinetic variability of MPA, from plasma protein binding and metabolic perspectives, in both pediatric and adult HSCT patients.…”