MPA protein binding in uremic plasma: Prediction of free fraction

H. U. Meier Kriesche, B. Kaplan, M. Korecka, S. Mulgaonkar, G. Friedman, K. Brayman, L. M. Shaw

    Research output: Contribution to journalArticlepeer-review


    The active form of Mycophenolate Mofetil (MMF) is Mycophenolic Acid (MPA). MPA is metabolized to its inactive glucuronide metabolite MPAG. Patients with renal failure have elevated MPAG concentrations. Free fraction and the free concentrations of MPA are increased in patients with renal failure. This study attempted to explore the nature of this decreased protein binding and develop a regression equation to predict free fraction. Plasma from ten uremic patients was obtained. Plasma from 7 healthy volunteers served as a control. MPA at a concentration of 30 μg/ml was added and then increasing amounts of MPAG were added to the samples. Total MPA and MPAG were measured by HPLC. Free MPA was measured by ultrafiltration. Multivariate regression was used utilizing free fraction (FF) as the dependent variable. MPAG (μg)ml 0 150 300 700 Controls*2.0±.13*2.3±.16*2.8±.22*4. 6±33 Uremic 4.0±.87 5.1±1.4 5.9±1.5 8.2±2.0*P<.05 FF=-13.3+2.8[ALB]+5.7[MPAG]*+3.5[1]**or [2]***R2=.75*MPAG in mg/ml**NL***Uremic Both uremia and MPAG contribute to the decreased protein binding of MPA. The FF of MPA can be approximated if MPAG concentration is known.

    Original languageEnglish (US)
    Number of pages1
    JournalClinical Pharmacology and Therapeutics
    Issue number2
    StatePublished - Jan 1 1999

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)


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