z-logo
Premium
Relationship of mycophenolic acid exposure to clinical outcome after hematopoietic cell transplantation
Author(s) -
Jacobson Pamala,
Rogosheske John,
Barker Juliet N.,
Green Kathleen,
Ng Juki,
Weisdorf Daniel,
Tan Ye,
Long Janel,
Remmel Rory,
Sawchuk Ronald,
McGlave Philip
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.08.009
Subject(s) - mycophenolic acid , dosing , medicine , transplantation , pharmacokinetics , cumulative incidence , immunosuppression , area under the curve , mycophenolate , ciclosporin , gastroenterology , hematopoietic stem cell transplantation , pharmacology , trough level , tacrolimus
Mycophenolate mofetil is used increasingly to provide immunosuppression after nonmyeloablative allogeneic hematopoietic cell transplantation. There is wide variability in the pharmacokinetics of mycophenolic acid (MPA), the active metabolite, and low concentrations are associated with rejection after organ transplantation. We hypothesized that low MPA was associated with poorer engraftment and a higher incidence of acute graft versus host disease. We evaluated the pharmacokinetics in 87 adult subjects undergoing nonmyeloablative‐related and nonmyeloablative‐unrelated hematopoietic cell transplantation who were receiving 1 g mycophenolate mofetil orally or intravenously every 12 hours plus cyclosporine (INN, ciclosporin). Subjects with an unbound MPA area under the curve (AUC) from 0 to 6 hours of less than 150 ng · h/mL had a higher cumulative incidence of grade II‐IV acute graft versus host disease than subjects with a greater AUC (68% versus 40%, P = .02). An unbound AUC from 0 to 12 hours of less than 300 ng · h/mL was also associated with more frequent acute graft versus host disease (58% versus 35%, P = .05). There was no association between graft versus host disease and trough concentrations ( P ≤ .62). A higher cumulative incidence of engraftment was associated with total MPA trough concentrations greater than 1 μg/mL ( P <.01). All engraftment failures occurred in the cord blood recipients. About one half of subjects were below the unbound AUC target after oral dosing with nearly a 5‐fold variability in AUC. Intravenous dosing achieved unbound targets better than oral dosing. The current practice of dosing with 1 g twice daily provides inadequate plasma concentrations in many patients, and doses of at least 3 g/d are likely necessary. Therapeutic monitoring of MPA concentrations with dose adjustment into the therapeutic target appears to be necessary for the most effective use of mycophenolate mofetil. Clinical Pharmacology & Therapeutics (2005) 78 , 486–500; doi: 10.1016/j.clpt.2005.08.009

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here