title: Mycophenolic acid pharmacokinetics during maintenance immunosuppression in African American and Caucasian renal transplant recipients.
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.
authors.affiliation: Pharmacotherapy Research Center, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14260-1200, USA. tornator@buffalo.edu
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Tornatore
authors.forename: Patcharaporn
authors.initials: P
authors.lastname: Sudchada
authors.forename: Kiran
authors.initials: K
authors.lastname: Dole
authors.forename: Robin
authors.initials: R
authors.lastname: DiFrancesco
authors.forename: Nicolae
authors.initials: N
authors.lastname: Leca
authors.forename: Aijaz C
authors.initials: AC
authors.lastname: Gundroo
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Danison
authors.forename: Kris
authors.initials: K
authors.lastname: Attwood
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Wilding
authors.forename: Julia
authors.initials: J
authors.lastname: Zack
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.forename: Rocco C
authors.initials: RC
authors.lastname: Venuto
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004764:Enterohepatic Circulation; D005260:Female; D020719:Glucuronides / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism; D044465:White People
chemical_list: D020719:Glucuronides; D007166:Immunosuppressive Agents; D011355:Prodrugs; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D009173:Mycophenolic Acid