Mycophenolate mofetil in islet cell transplant: variable pharmacokinetics but good correlation between total and unbound concentrations.
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 x 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 x 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 (r2 = 0.94). Total mycophenolic acid trough concentration and total AUC(0-12) were modestly correlated (r2 = 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.
Jacobson
Pamala A
PA
Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Green
Kathleen G
KG
Hering
Bernhard J
BJ
D000328:Adult; D019540:Area Under Curve; D005260:Female; D020719:Glucuronides / Q000493:pharmacokinetics; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016381:Islets of Langerhans Transplantation; D008137:Longitudinal Studies; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011485:Protein Binding; D020123:Sirolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
D020719:Glucuronides; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus