Volumetric Absorptive Microsampling Combined with Mass Spectrometry to Support Pharmacokinetically-Guided Precision Dosing of Mycophenolate Mofetil in Pediatric Lupus Nephritis Patients.

Abstract

Background: The immunosuppressant mycophenolate mofetil (MMF) is used off-label in patients with systemic lupus erythematosus (SLE) although the optimum dosing regimen is not well established. This study evaluated the use of volumetric absorptive microsampling (VAMS) for capillary whole blood collected by finger-prick, combined with tandem mass spectrometry and limited timepoint sampling to determine concentrations of mycophenolic acid (MPA) and its glucuronide conjugate, MPA-7-O-glucuronide (MPAG) in SLE patients. This approach permitted pharmacokinetically guided optimized dosing of MPA.

Methods: Blood was collected by finger-prick and venipuncture from patients (n = 10) at trough, 30, and 120 min postdosing with MMF. MPA/MPAG concentrations were assayed from dried VAMS devices by stable-isotope dilution LC-MS-MS and compared to MPA/MPAG concentrations measured in plasma by high performance liquid chromatography after adjusting for hematocrit.

Results: There was no significant difference between MPA concentrations from VAMS-collected dried capillary blood hematocrit-adjusted and those for plasma. The area under the concentration-time curve (AUC) estimated from plasma equivalent concentrations converted from capillary VAMS results correlated well with the AUC estimated from plasma concentrations (R2 = 0.97).

Conclusions: The plasma pharmacokinetics of MMF metabolites can be reliably estimated from concentrations in capillary blood using VAMS devices and only 3 timed collections. Sampling whole blood by finger-prick, a less invasive approach for patients, coupled with the specificity of LC-MS/MS can be accurately used as an alternative to plasma sampling to establish the optimal dosing regimen of MMF for patients with SLE based on dried blood samples.