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Tacrolimus Exposure in Obese Patients: A Case-Control Study in Kidney Transplantation.

Abstract：

BACKGROUND:Tacrolimus pharmacokinetics in obese patients have been poorly studied. Herein, the authors explored the impact of obesity on tacrolimus exposure in kidney transplant recipients (KTRs) and estimated a more suitable initial dosage in this population. METHODS:A retrospective, observational, monocentric case-control study was performed in obese (Ob) KTRs (BMI > 30 kg/m) who received tacrolimus between 2013 and 2017 (initial dose: 0.15 mg/kg/day) (actual weight). Non-obese (Nob) controls (BMI < 30 kg/m) were matched for age and sex. Weekly centralized monitoring of tacrolimus trough levels was done by LC-MS/MS until the 3 month (M3). Target trough levels were set between 8-10 ng/mL. All patients received anti-lymphocyte globulin, corticosteroids, and mycophenolate mofetil. RESULTS:Of the 541 KTRs, 28 tacrolimus-treated Ob patients were included and compared with 28 NOb-matched controls. With a mean of 22 assays/patient, tacrolimus trough levels were higher in Ob patients (mean 9.9 vs 8.7 ng/mL; P = 0.008); the weight-related dose of Tac was lower at M3 (mean 0.10 vs 0.13 mg/kg/day, P < 0.0001). The tacrolimus concentration to dose (C0/D) was higher in the Ob cohort (mean 116 vs 76 [ng/mL]/[mg/kg/day]; P = 0.001). In Ob patients, a mean decrease of -4.6 mg/day in the 3 months following tacrolimus initiation was required (vs -1.12 in NOb; P = 0.001) to remain within the therapeutic range. Obesity, high mycophenolate mofetil daily dose at M3, and CYP3A5 expression were independently associated with higher tacrolimus exposure. Four dose-adaptation strategies were simulated and compared with the study results. CONCLUSIONS:An initial dose calculation based on either ideal or lean body weight may allow for faster achievement of tacrolimus trough level targets in Ob KTRs, who are at risk of overexposure when tacrolimus is initiated at 0.15 mg/kg/day. A prospective study is required to validate alternative dose calculation strategies in these patients.

journal_name

Ther Drug Monit

journal_title

Therapeutic drug monitoring

authors

Robert V,Manos-Sampol E,Manson T,Robert T,Decourchelle N,Anne-Sophie G,Quaranta S,Moal V,Legris T

doi

10.1097/FTD.0000000000000820

subject

Has Abstract

pub_date

2020-10-05 00:00:00

eissn

0163-4356

issn

1536-3694

pub_type

杂志文章

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Tacrolimus Exposure in Obese Patients: A Case-Control Study in Kidney Transplantation.