PMID- 25511793
OWN - NLM
STAT- MEDLINE
DCOM- 20151110
LR  - 20221207
IS  - 1179-1926 (Electronic)
IS  - 0312-5963 (Print)
IS  - 0312-5963 (Linking)
VI  - 54
IP  - 4
DP  - 2015 Apr
TI  - Influence of sex and race on mycophenolic acid pharmacokinetics in stable African 
      American and Caucasian renal transplant recipients.
PG  - 423-34
LID - 10.1007/s40262-014-0213-7 [doi]
AB  - BACKGROUND AND OBJECTIVES: 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. CONCLUSION: 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.
FAU - Tornatore, Kathleen M
AU  - Tornatore KM
AD  - 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.
FAU - Meaney, Calvin J
AU  - Meaney CJ
FAU - Wilding, Gregory E
AU  - Wilding GE
FAU - Chang, Shirley S
AU  - Chang SS
FAU - Gundroo, Aijaz
AU  - Gundroo A
FAU - Cooper, Louise M
AU  - Cooper LM
FAU - Gray, Vanessa
AU  - Gray V
FAU - Shin, Karen
AU  - Shin K
FAU - Fetterly, Gerald J
AU  - Fetterly GJ
FAU - Prey, Joshua
AU  - Prey J
FAU - Clark, Kimberly
AU  - Clark K
FAU - Venuto, Rocco C
AU  - Venuto RC
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
GR  - R01 AG056392/AG/NIA NIH HHS/United States
GR  - R21 DK077325/DK/NIDDK NIH HHS/United States
GR  - R21DK077325-01A1/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Clin Pharmacokinet
JT  - Clinical pharmacokinetics
JID - 7606849
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Glucuronides)
RN  - 0 (Immunosuppressive Agents)
RN  - 54TS5J9T0K (mycophenolic acid glucuronide)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adult
MH  - *Black or African American
MH  - Aged
MH  - Antibiotics, Antineoplastic/adverse effects/pharmacokinetics
MH  - Cross-Sectional Studies
MH  - Drug Interactions
MH  - Drug Therapy, Combination
MH  - Female
MH  - Glucuronides/adverse effects/*pharmacokinetics
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage
MH  - *Kidney Transplantation
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Mycophenolic Acid/adverse effects/*analogs & derivatives/*pharmacokinetics
MH  - Sex Factors
MH  - Tacrolimus/*administration & dosage
MH  - Transplant Recipients
MH  - *White People
PMC - PMC4435744
MID - NIHMS649537
EDAT- 2014/12/17 06:00
MHDA- 2015/11/11 06:00
PMCR- 2016/04/01
CRDT- 2014/12/17 06:00
PHST- 2014/12/17 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/11/11 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - 10.1007/s40262-014-0213-7 [doi]
PST - ppublish
SO  - Clin Pharmacokinet. 2015 Apr;54(4):423-34. doi: 10.1007/s40262-014-0213-7.