title: Influence of sex and race on mycophenolic acid pharmacokinetics in stable African American and Caucasian renal transplant recipients.
abstract: OBJECTIVE
  No evaluation of sex and race influences on mycophenolic acid (MPA) pharmacokinetics and adverse effects (AEs) during enteric-coated mycophenolate sodium (ECMPS) and tacrolimus immunosuppression are available. The primary objective of this study was to investigate the influence of sex and race on MPA and MPA glucuronide (MPAG) pharmacokinetics in stable renal transplant recipients receiving ECMPS and tacrolimus
  
  
  METHODS
  The pharmacokinetics of MPA and MPAG and their associated gastrointestinal AEs were investigated in 67 stable renal transplant recipients: 22 African American males (AAMs), 13 African American females (AAFs), 16 Caucasian males (CMs), and 16 Caucasian females (CFs) receiving ECMPS and tacrolimus. A validated gastrointestinal AE rating included diarrhea, dyspepsia, vomiting, and acid-suppressive therapy was completed. Apparent clearance, clearance normalized to body mass index (BMI), area under the concentration-time curve from time zero to 12 h (AUC12) and dose-normalized AUC12 (AUC*) were determined using a statistical model that incorporated gastrointestinal AE and clinical covariates.
  
  
  RESULTS
  Males had more rapid apparent MPA clearance (CMs 13.8 ± 6.27 L/h vs. AAMs 10.2 ± 3.73 L/h) than females (CFs 8.70 ± 3.33 L/h and AAFs 9.71 ± 3.94 L/h; p = 0.014) with a race-sex interaction (p = 0.043). Sex differences were observed in MPA clearance/BMI (p = 0.033) and AUC* (p = 0.033). MPA AUC12 was greater than 60 mg·h/L in 57 % of renal transplant recipients (RTR) with 71 % of patients demonstrating gastrointestinal AEs and a higher score noted in females. In all patients, females exhibited 1.40-fold increased gastrointestinal AE scores compared with males (p = 0.024). Race (p = 0.044) and sex (p = 0.005) differences were evident with greater MPAG AUC12 in AAFs and CFs.
  
  
  CONCLUSIONS
  Sex and race differences were evident, with females having slower MPA clearance, higher MPAG AUC12, and more severe gastrointestinal AEs. These findings suggest sex and race should be considered during MPA immunosuppression.
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Immunosuppressive Pharmacology Research Program, Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, 701 Ellicott Street, Buffalo, NY, 14203, USA, tornator@buffalo.edu.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Tornatore
authors.forename: Calvin J
authors.initials: CJ
authors.lastname: Meaney
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Wilding
authors.forename: Shirley S
authors.initials: SS
authors.lastname: Chang
authors.forename: Aijaz
authors.initials: A
authors.lastname: Gundroo
authors.forename: Louise M
authors.initials: LM
authors.lastname: Cooper
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gray
authors.forename: Karen
authors.initials: K
authors.lastname: Shin
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Fetterly
authors.forename: Joshua
authors.initials: J
authors.lastname: Prey
authors.forename: Kimberly
authors.initials: K
authors.lastname: Clark
authors.forename: Rocco C
authors.initials: RC
authors.lastname: Venuto
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics; D003430:Cross-Sectional Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D020719:Glucuronides / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D012737:Sex Factors; D016559:Tacrolimus / Q000008:administration & dosage*; D066027:Transplant Recipients; D044465:White People
chemical_list: D000903:Antibiotics, Antineoplastic; D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid; D016559:Tacrolimus