TY - JOUR
T1 - Racial comparisons of everolimus pharmacokinetics and pharmacodynamics in adult kidney transplant recipients
AU - Taber, David J.
AU - Belk, Lindsey
AU - Meadows, Holly
AU - Pilch, Nicole
AU - Fleming, James
AU - Srinivas, Titte
AU - McGillicuddy, John
AU - Bratton, Charles
AU - Chavin, Kenneth
AU - Baliga, Prabhakar
N1 - Over the past few decades, acute rejection rates have dramatically decreased in kidney transplantation. This is largely due to improved more sensitive techniques with HLA antibody detection and enhanced induction and maintenance immunosuppression regimens.
PY - 2013/12
Y1 - 2013/12
N2 - BACKGROUND:: There is limited data analyzing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of everolimus (EVR) between African Americans and Caucasians. The purpose of this study was to determine and compare the EVR PKs and concentration-associated efficacy and toxicity in African American and Caucasian adult kidney transplant recipients. METHODS:: This was a retrospective PK and PD analysis of all patients who received EVR at the Medical University of South Carolina Transplant Center between 2006 and 2012. RESULTS:: Forty-three patients received EVR (22 African Americans, 21 Caucasians). Baseline demographics, immunosuppression, and immunologic risk were similar between races, except for preexisting hypertension, deceased donor type, and cold ischemic time, which were higher in African American patients. PK analysis revealed that African American patients received higher initial EVR doses (2.1 ± 0.8 versus 1.6 ± 0.6 mg/d, P = 0.036), leading to higher early EVR concentrations (EVR >6 ng/mL during the first 60 days: 36% versus 10%, P = 0.037). Efficacy analysis demonstrated similar EVR effects on acute rejection rates (9% versus 10%, P = 0.961), chronic allograft changes (18% versus 14%, P = 0.729), and renal function, with both groups having improved creatinine clearance with EVR therapy (ΔeGFR: 27 versus 12 mL·min·1.73 m). Toxicity analysis demonstrated that African American patients had a trend toward higher rates of EVR discontinuation (46% versus 19%, P = 0.065) and significantly more diarrhea/gastrointestinal intolerance (73% versus 38%, P = 0.022). CONCLUSIONS:: These results demonstrate EVR therapy is effective at preventing rejection and improving graft function in both African American and Caucasian adult renal transplant patients. Conflicting with previous mammalian target of rapamycin PK/PD analyses in African American patients, this study cohort demonstrated higher early EVR levels in the African American patients.
AB - BACKGROUND:: There is limited data analyzing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of everolimus (EVR) between African Americans and Caucasians. The purpose of this study was to determine and compare the EVR PKs and concentration-associated efficacy and toxicity in African American and Caucasian adult kidney transplant recipients. METHODS:: This was a retrospective PK and PD analysis of all patients who received EVR at the Medical University of South Carolina Transplant Center between 2006 and 2012. RESULTS:: Forty-three patients received EVR (22 African Americans, 21 Caucasians). Baseline demographics, immunosuppression, and immunologic risk were similar between races, except for preexisting hypertension, deceased donor type, and cold ischemic time, which were higher in African American patients. PK analysis revealed that African American patients received higher initial EVR doses (2.1 ± 0.8 versus 1.6 ± 0.6 mg/d, P = 0.036), leading to higher early EVR concentrations (EVR >6 ng/mL during the first 60 days: 36% versus 10%, P = 0.037). Efficacy analysis demonstrated similar EVR effects on acute rejection rates (9% versus 10%, P = 0.961), chronic allograft changes (18% versus 14%, P = 0.729), and renal function, with both groups having improved creatinine clearance with EVR therapy (ΔeGFR: 27 versus 12 mL·min·1.73 m). Toxicity analysis demonstrated that African American patients had a trend toward higher rates of EVR discontinuation (46% versus 19%, P = 0.065) and significantly more diarrhea/gastrointestinal intolerance (73% versus 38%, P = 0.022). CONCLUSIONS:: These results demonstrate EVR therapy is effective at preventing rejection and improving graft function in both African American and Caucasian adult renal transplant patients. Conflicting with previous mammalian target of rapamycin PK/PD analyses in African American patients, this study cohort demonstrated higher early EVR levels in the African American patients.
KW - African American
KW - Everolimus
KW - Kidney transplant
KW - Pharmacodynamics
KW - Pharmacokinetics
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U2 - 10.1097/FTD.0b013e31829a7a7c
DO - 10.1097/FTD.0b013e31829a7a7c
M3 - Article
C2 - 24061443
SN - 0163-4356
VL - 35
SP - 753
EP - 759
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
IS - 6
ER -