Validation of tacrolimus equation to predict troughs using genetic and clinical factors.
OBJECTIVE
Tacrolimus is an immunosuppressant used in transplantation. This article reports the validation of the authors' recently developed genetics-based tacrolimus equation that predicts troughs.


METHODS
Validation was performed in an independent cohort of 795 kidney transplant recipients receiving tacrolimus. The performance of the equation to predict initial troughs was assessed by calculating the bias and precision of the equation. For all troughs in the first 6 months post-transplant, a comparison was made between the troughs predicted using the equation versus those predicted using a basic apparent clearance model with no covariates.


RESULTS
For initial troughs, the equation had a low bias (0.2 ng/ml) and high precision (1.8 ng/ml). For all troughs, the equation predicted troughs significantly better than the basic apparent clearance model.


CONCLUSIONS
The tacrolimus equation had good bias and precision in predicting initial troughs and performed better than a basic apparent clearance model for all the troughs.
Department of Experimental & Clinical Pharmacology, 717 Delaware Street, University of Minnesota, Minneapolis, MN 55455, USA.
Chaitali
C
Passey
Angela K
AK
Birnbaum
Richard C
RC
Brundage
David P
DP
Schladt
William S
WS
Oetting
Robert E
RE
Leduc
Ajay K
AK
Israni
Weihua
W
Guan
Arthur J
AJ
Matas
Pamala A
PA
Jacobson
D000328:Adult; D054316:Biomarkers, Pharmacological; D002986:Clinical Trials as Topic; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage*
D054316:Biomarkers, Pharmacological; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus