NDLI: Evaluation of inosin-5'-monophosphate dehydrogenase activity during maintenance therapy with tacrolimus.

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Evaluation of inosin-5'-monophosphate dehydrogenase activity during maintenance therapy with tacrolimus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Maiguma, T. Yosida, T. Otsubo, K. Okabe, Y. Sugitani, A. Tanaka, M. Oishi, R. Teshima, D.
Description	Country affiliation: Japan Author Affiliation: Maiguma T ( Department of Clinical Pharmacy, School of Pharmacy, Shujitsu University, Okayama, Japan.)
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 beta-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(50) 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.
File Format	HTM / HTML
ISSN	02694727
Issue Number	1
Volume Number	35
e-ISSN	13652710
Journal	Journal of Clinical Pharmacy and Therapeutics
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2010-02-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Therapeutics Discipline Pharmacology Drug Monitoring Methods Enzyme Inhibitors Pharmacokinetics Imp Dehydrogenase Blood Immunosuppressive Agents Mycophenolic Acid Analogs & Derivatives Prodrugs Tacrolimus Adult Biomarkers, Pharmacological Chromatography, High Pressure Liquid Drug Interactions Drug Therapy, Combination Therapeutic Use Female Humans Antagonists & Inhibitors Kidney Transplantation Kinetics Leukocytes, Mononuclear Chemistry Drug Effects Enzymology Male Middle Aged Reproducibility Of Results Ribonucleotides Analysis Young Adult Evaluation Studies Journal Article
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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