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Mycophenolate Mofetil in Islet Cell Transplant: Variable Pharmacokinetics but Good Correlation Between Total and Unbound Concentrations
Author(s) -
Jacobson Pamala A.,
Green Kathleen G.,
Hering Bernhard J.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005278599
Subject(s) - mycophenolic acid , pharmacokinetics , mycophenolate , trough concentration , pharmacology , medicine , therapeutic drug monitoring , transplantation , immunosuppressive drug , area under the curve , chemistry , urology
The authors investigated the pharmacokinetics of mycophenolic acid over 1 year in 8 Caucasian women undergoing islet cell transplantation. Total mycophenolic acid AUC 0‐12 mcg•h/mL before day 60 was 62.1–67.8, declining to 33.6–64.7 thereafter (P = .61). Median total trough concentrations were 1.16–2.90 mcg/mL. Unbound AUC 0‐12 was 412–673 ng•h/mL and did not change over time (P = .30). Median percent unbound mycophenolic acid was 0.95% of total concentrations. Individual unbound and total mycophenolic acid concentrations were highly correlated (r 2 = 0.94). Total mycophenolic acid trough concentration and total AUC 0‐12 were modestly correlated (r 2 = 0.65). Intra‐ and interpatient variability of systemic mycophenolic acid exposure was high. Six patients required dose reductions prior to day 60 due to adverse effects. All subjects achieved insulin independence; 3 later lost graft function. The trend toward higher exposure in the early periods followed by dose reductions suggests that lower initial doses and therapeutic drug monitoring may be necessary.