The Application of Inosine 5′-Monophosphate Dehydrogenase Activity Determination in Peripheral Blood Mononuclear Cells for Monitoring Mycophenolate Mofetil Therapy in Children with Nephrotic Syndrome

Pharmaceuticals

Jacek Zachwieja¹  Danuta Ostalska-Nowicka¹  Honorata Wziętek²  Alicja Jóźwiak²  Joanna Sobiak² 

[1] Department of Pediatric Nephrology and Hypertension, Poznan University of Medical Sciences, 60-572 Poznań, Poland;Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 60-781 Poznań, Poland;

关键词: mycophenolic acid;    inosine-5′-monophosphate dehydrogenase activity;    pediatric patients;    HPLC method;    therapeutic drug monitoring;    nephrotic syndrome;   

DOI  :  10.3390/ph13080200

来源: DOAJ

【 摘 要 】

In pediatric nephrotic syndrome, recommended mycophenolic acid (MPA) pharmacokinetics are higher than those for transplant recipients. In MPA therapeutic monitoring, inosine-5′-monophosphate dehydrogenase (IMPDH) activity may be useful. We modified the method established for renal transplant recipients and determined IMPDH activity in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and children (4–16 years) with nephrotic syndrome treated with mycophenolate mofetil (MMF). From children, four blood samples were collected, and MPA concentrations were also determined. IMPDH activity was calculated using xanthosine monophosphate (XMP) normalized with adenosine monophosphate (AMP), both determined with the HPLC-UV method. The modified method was accurate, precise, and linear for AMP and XMP within 0.50–50.0 μmoL/L. Mean IMPDH activity in volunteers was 45.97 ± 6.24 µmoL·s⁻¹·moL⁻¹ AMP, whereas for children, the values were variable and amounted to 39.23 ± 27.40 µmoL·s⁻¹·moL⁻¹ AMP and 17.97 ± 15.24 µmoL·s⁻¹·moL⁻¹ AMP before the next MMF dose and 1 h afterward, respectively. The modified method may be applied to IMPDH activity determination in children with nephrotic syndrome treated with MMF. IMPDH activity should be determined after one thawing of PBMCs due to the change in AMP and XMP concentrations after subsequent thawing. For children, the lowest IMPDH activity was observed concomitantly with the highest MPA concentration.

【 授权许可】

Unknown