Equivalent pharmacokinetics of mycophenolate mofetil in African-American and Caucasian male and female stable renal allograft recipients

Am J Transplant. 2003 Dec;3(12):1581-6. doi: 10.1046/j.1600-6135.2003.00243.x.

Abstract

African-American (AA) renal transplant recipients require higher doses of mycophenolate mofetil (MMF) than Caucasians. A hypothesized pharmacokinetic (PK) difference was tested in stable renal transplant recipients. Whole blood was collected before, and 20, 40 and 75 min, and 2, 3, 4, 6, 8 and 12 h after the MMF dose. Mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were analyzed using HPLC. Analysis of variance was performed for the primary end-points of dose-adjusted PK parameters AUC0-12 and Cmax of MPA using log-transformed values. Differences between races and genders were estimated: 90% confidence intervals (CI) were calculated. Back-transformation gave estimates of the race and gender ratio and their CI. Equivalence of the groups was determined if the 90% confidence limits were included in the interval (0.80, 1.25). The calculated PK parameters were comparable among the four subgroups (Caucasian, AA, Male, Female). The 90% CIs for the ratio of dose-adjusted AUC0-12 of MPA between races were between 89.7 and 112.9%. There were no race, gender or race-by-gender effects (p-values = 0.196) nor differences between diabetics and nondiabetics. This study demonstrates that dosing requirement for MMF in AA and Caucasians is unlikely to be related to different exposures to MPA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • African Americans
  • Aged
  • European Continental Ancestry Group
  • Female
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacokinetics*

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid