Mycophenolic acid pharmacokinetics during maintenance immunosuppression in African American and Caucasian renal transplant recipients

J Clin Pharmacol. 2011 Aug;51(8):1213-22. doi: 10.1177/0091270010382909. Epub 2011 Jan 5.

Abstract

Renal transplant recipients exhibit variability in mycophenolic acid (MPA) and MPA glucuronide (MPAG) pharmacokinetics, which are influenced by clinical and demographic factors. Racial influence on MPA and MPAG pharmacokinetics was investigated in 53 patients: 17 African American males, 22 Caucasian males, and 14 females receiving mycophenolate mofetil (MMF) and cyclosporine. A 12-hour steady-state pharmacokinetic study was conducted. Enterohepatic circulation of MPA was characterized by a second plasma concentration peak and was included in a novel statistical model with MPAG. MPA clearance in African American males was 26.5 ± 14.4 L/h versus 17.9 ± 6.1 L/h in Caucasian males (P = .035) and 16.1 ± 4.6 L/h in Caucasian females (P = .024) with no difference noted in MPA troughs. Enterohepatic circulation occurred less frequently in African American males (23%) compared with Caucasian males (42%) and Caucasian females (50%) (P > .05). Cyclosporine exposure was correlated with MPA and MPAG pharmacokinetics, whereas creatinine clearance influenced MPAG pharmacokinetics. A racial difference was noted with more rapid MPA clearance in African American males compared with Caucasians. The results support differential MPA dosing and the role of therapeutic drug monitoring in addition to considering the influence of renal function and concurrent immunosuppressives on MPA and MPAG pharmacokinetics.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Black or African American*
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Enterohepatic Circulation
  • Female
  • Glucuronides / blood
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects*
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Models, Biological
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / blood
  • Mycophenolic Acid / pharmacokinetics
  • Mycophenolic Acid / therapeutic use
  • Prodrugs / pharmacokinetics*
  • Prodrugs / therapeutic use
  • Renal Insufficiency / etiology
  • Renal Insufficiency / metabolism
  • White People*

Substances

  • Glucuronides
  • Immunosuppressive Agents
  • Prodrugs
  • mycophenolic acid glucuronide
  • Cyclosporine
  • Mycophenolic Acid