title: Improved Tacrolimus Target Concentration Achievement Using Computerized Dosing in Renal Transplant Recipients--A Prospective, Randomized Study.
abstract: BACKGROUND
  Early after renal transplantation, it is often challenging to achieve and maintain tacrolimus concentrations within the target range. Computerized dose individualization using population pharmacokinetic models may be helpful. The objective of this study was to prospectively evaluate the target concentration achievement of tacrolimus using computerized dosing compared with conventional dosing performed by experienced transplant physicians.
  
  
  METHODS
  A single-center, prospective study was conducted. Renal transplant recipients were randomized to receive either computerized or conventional tacrolimus dosing during the first 8 weeks after transplantation. The median proportion of tacrolimus trough concentrations within the target range was compared between the groups. Standard risk (target, 3-7 μg/L) and high-risk (8-12 μg/L) recipients were analyzed separately.
  
  
  RESULTS
  Eighty renal transplant recipients were randomized, and 78 were included in the analysis (computerized dosing (n = 39): 32 standard risk/7 high-risk, conventional dosing (n = 39): 35 standard risk/4 high-risk). A total of 1711 tacrolimus whole blood concentrations were evaluated. The proportion of concentrations per patient within the target range was significantly higher with computerized dosing than with conventional dosing, both in standard risk patients (medians, 90% [95% confidence interval {95% CI}, 84-95%] vs 78% [95% CI, 76-82%], respectively, P < 0.001) and in high-risk patients (medians, 77% [95% CI, 71-80%] vs 59% [95% CI, 40-74%], respectively, P = 0.04).
  
  
  CONCLUSIONS
  Computerized dose individualization improves target concentration achievement of tacrolimus after renal transplantation. The computer software is applicable as a clinical dosing tool to optimize tacrolimus exposure and may potentially improve long-term outcome.
authors.affiliation: 1 Department of Transplant Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 2 Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 3 School of Pharmacy, University of Oslo, Oslo, Norway. 4 Laboratory of Applied Pharmacokinetics, Children's Hospital Los Angeles, Los Angeles, CA. 5 Department of Pharmacology, Oslo University Hospital, Oslo, Norway. 6 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Størset
authors.forename: Anders
authors.initials: A
authors.lastname: Åsberg
authors.forename: Morten
authors.initials: M
authors.lastname: Skauby
authors.forename: Michael
authors.initials: M
authors.lastname: Neely
authors.forename: Stein
authors.initials: S
authors.lastname: Bergan
authors.forename: Sara
authors.initials: S
authors.lastname: Bremer
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtvedt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003198:Computer Simulation; D005260:Female; D005838:Genotype; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000601:surgery*; D012307:Risk Factors; D012984:Software; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus