title: Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.
abstract: BACKGROUND
  Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight.
  
  
  METHODS
  For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based onCYP3A5genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing.
  
  
  RESULTS
  Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set.
  
  
  CONCLUSIONS
  This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients.
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Andrews
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Brenda C M
authors.initials: BC
authors.lastname: de Winter
authors.affiliation: Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Jiang-Tao
authors.initials: JT
authors.lastname: Tang
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Nauras
authors.initials: N
authors.lastname: Shuker
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Rachida
authors.initials: R
authors.lastname: Bouamar
authors.affiliation: Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Birgit C P
authors.initials: BC
authors.lastname: Koch
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink