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Evaluation of inosin-5′-monophosphate dehydrogenase activity during maintenance therapy with tacrolimus.
- Source :
- Journal of Clinical Pharmacy & Therapeutics; Feb2010, Vol. 35 Issue 1, p79-85, 7p, 2 Charts, 5 Graphs
- Publication Year :
- 2010
-
Abstract
- Objectives: The aim of this study was to identify a target range for inosin-5′-monophosphate dehydrogenase (IMPDH) activity in maintenance therapy with tacrolimus (TCL), and to apply the measurement of IMPDH activity to the therapeutic drug monitoring for mycophenolate mofetil (MMF). Methods: Eleven patients with renal transplants and 10 healthy volunteers were investigated. All patients were treated with a combination of TCL, steroid and MMF for 2 months after transplantation, and were in stable and good condition. IMPDH activity was determined indirectly by measuring xanthosine 5′-monophophate in cell lysates supplemented with IMP and β-nicotine adenine dinucleotide using an high-performance liquid chromatography (HPLC) method. Results: The within-run reproducibility of the assay was excellent, with relative standard deviation (RSD) values of 0·41–4·08%. The mean differences between the spiked concentrations of xanthosine 5′-monophophate and their real values (mean relative errors; MREs) were within a range of 2·66–8·89%, showing good accuracy. The interday RSD values were 1·51–6·12% and MREs ranged from 2·10% to 8·89%. Cell lysates showed a 5–6 nmol/L IC<subscript>50</subscript> mycophenolic acid (MPA) concentration. TCL, cyclosporine and prednisolone did not affect IMPDH activity. The peak MPA concentration was achieved at 1 h after dosing. IMPDH activity decreased to 75% and 67% at 1 and 2 h after dosing respectively. Therefore, the inhibition rates of MPA against IMPDH activity may be adequate at 25–40% in TCL maintenance therapy. Conclusion: Inosin-5′-monophosphate dehydrogenase activity in cell lysates could be reliably determined by HPLC. A 25–40% inhibition of IMPDH activity may be an appropriate range for preventing rejection with MPF but this requires further validation using larger studies with harder outcomes such as rejection episodes. [ABSTRACT FROM AUTHOR]
- Subjects :
- DEHYDROGENASES
THERAPEUTICS
TACROLIMUS
DRUG analysis
IMMUNOSUPPRESSIVE agents
Subjects
Details
- Language :
- English
- ISSN :
- 02694727
- Volume :
- 35
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Clinical Pharmacy & Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 47339126
- Full Text :
- https://doi.org/10.1111/j.1365-2710.2009.01072.x