Background/Purpose: Mycophenolic acid (MPA) is the biologically active metabolite of mycophenolate mofetil (MMF), a widely used immunosuppressant in the treatment of childhood-onset systemic lupus erythematosus (cSLE). In our center, 54% of our cSLE patients are of Hispanic ethnicity. Hispanic cSLE patients are predisposed to higher SLE disease activity and risk for increased morbidity but have also been found to respond well to MMF. Published cSLE MPA PK studies include mainly Caucasian or African-American patients. The objective of this ongoing study is to describe the pharmacokinetics (PK) of MPA in a cohort of Hispanic cSLE patients at a single center.

Methods: The PK of MPA and its glucuronide metabolites (MPA glucuronide/ MPAG and Acyl MPA glucuronide/ AcMPAG) was evaluated in cSLE patients (n=6; all female and Hispanic; age 13-18 years) on a stable MMF regimen (1,500-2,000 mg/day) (Table 1). Blood samples for PK analysis were collected at 4 time points: prior to MMF morning dose administration (trough), 20 minutes, 1 hour, and 3 hours post-MMF administration. Exposure to drug (PK) was measured by the area under the curve of MPA concentration plotted against time. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Results: The plasma concentration-time profiles of MPA, MPAG, and AcMPAG are shown in Figure 1. The PK parameters (mean ± SD) were: maximum MPA concentration (C_max) of 12.8 ± 7 µg/ml (55% coefficient of variation, CV), time to reach C_max (T_max) of 0.8 ± 0.4 hrs (44.5% CV), and AUC_{0-3 h} of 23.7 ± 12.3 µg*hr/ml (51.9% CV). There was noted improvement and decline in SLEDAI scores averaged over time after MMF therapy initiation (Table 1).  

Conclusion: Our study in an all-Hispanic cSLE patient cohort demonstrated MPA PK parameters which are consistent with currently published literature on MPA PK in cSLE patients. Substantial inter-patient variability in MPA PK was observed, highlighting the need for further studies on individualized MMF dosing strategies in cSLE.    

Table 1. Demographic and clinical characteristics of patients with childhood-onset SLE at the time of the PK sampling visit.

Note:

SD – standard deviation

*Change in disease activity measures averaged over time using the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index)

† MTA-SLEDAI _Pre-MMF – time-adjusted mean of SLEDAI scores measured up to 6 months prior to initiation of MMF therapy

‡ MTA-SLEDAI _Post-MMF – time-adjusted mean of SLEDAI scores measured starting at least 2 weeks after initiation of MMF therapy until PK sampling date     Figure 1. Mean MPA, MPAG, and AcMPAG Plasma Concentration (Mean ± SE) -Time Profiles