Tacrolimus monitoring by simplified sparse sampling under the concentration time curve.
The purpose of this study was to determine which tacrolimus pharmacokinetic parameters best predicted efficacy in kidney transplantation. Blood tacrolimus levels at 0, 1, 2, 3, and 4 hours postdose were measured in 28 kidney transplants. All received tacrolimus-based triple-drug therapy with mychophenolate mofetil and prednisone. Associations between blood concentrations at each sampling time point and the area under the curve (AUC) 0-4 were measured by Pearson's correlation coefficients. Tacrolimus dosing was based on C0 not AUC. AUC and blood concentrations at each sampling time were retrospectively compared with C0 as predictor of acute rejection and nephrotoxicity. Although tacrolimus C0 correlated with AUC0-4 (r =.86), correlations were higher with C2 and C3 (r =.96 and r =.94, respectively). C0 levels were not significantly different in six patients with acute rejection and 23 patients without. There was a trend toward lower tacrolimus C3 in patients with AR than without AR (P =.06). C2 and C3 correlate better with AUC0-4 than C0. Early tacrolimus C3 levels may be a better than C0 as a predictor of efficacy.
Balbontin
F G
FG
Kidney Transplant Program, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada. fbalbont@dal.ca
Kiberd
B
B
Squires
J
J
Singh
D
D
Fraser
A
A
Belitsky
P
P
Lawen
J
J
D000328:Adult; D019540:Area Under Curve; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors
D007166:Immunosuppressive Agents; D016559:Tacrolimus