title: Equivalent pharmacokinetics of mycophenolate mofetil in African-American and Caucasian male and female stable renal allograft recipients.
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.
authors: Indiana University, Indianapolis, IN, USA. mpescov@iupui.edu
authors: Mark D
authors: MD
authors: Pescovitz
authors: Antonio
authors: A
authors: Guasch
authors: Robert
authors: R
authors: Gaston
authors: P
authors: P
authors: Rajagopalan
authors: Stephen
authors: S
authors: Tomlanovich
authors: Samuel
authors: S
authors: Weinstein
authors: Ginny L
authors: GL
authors: Bumgardner
authors: Larry
authors: L
authors: Melton
authors: Patricia Sanwald
authors: PS
authors: Ducray
authors: Ludger
authors: L
authors: Banken
authors: Joanna
authors: J
authors: Hall
authors: Bruno X
authors: BX
authors: Boutouyrie
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D044465:White People
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid