A limited sampling strategy for tacrolimus in renal transplant patients.
OBJECTIVE
To develop and validate limited sampling strategy (LSS) equations to estimate area under the curve (AUC(0-12)) in renal transplant patients.


METHODS
Twenty-nine renal transplant patients (3-6 months post transplant) who were at steady state with respect to tacrolimus kinetics were included in this study. The blood samples starting with the predose (trough) and collected at fixed time points for 12 h were analysed by microparticle enzyme immunoassay. Linear regression analysis estimated the correlations of tacrolimus concentrations at different sampling time points with the total measured AUC(0-12). By applying multiple stepwise linear regression analysis, LSS equations with acceptable correlation coefficients (R(2)), bias and precision were identified. The predictive performance of these models was validated by the jackknife technique.


RESULTS
Three models were identified, all with R(2) > or = 0.907. Two point models included one with trough (C(0)) and 1.5 h postdose (C(1.5)), another with trough and 4 h postdose. Increasing the number of sampling time points to more than two increased R(2) marginally (0.951 to 0.990). After jackknife validation, the two sampling time point (trough and 1.5 h postdose) model accurately predicted AUC(0-12). Regression coefficient R(2) = 0.951, intraclass correlation = 0.976, bias [95% confidence interval (CI)] 0.53% (-2.63, 3.69) and precision (95% CI) 6.35% (4.36, 8.35).


CONCLUSIONS
The two-point LSS equation [AUC(0-12) = 19.16 + (6.75.C(0)) + (3.33.C1.5)] can be used as a predictable and accurate measure of AUC(0-12) in stable renal transplant patients prescribed prednisolone and mycophenolate.
Mathew
Binu S
BS
Clinical Pharmacology Unit, Department of Biostatistics and Clinical Pharmacology, Christian Medical College, Vellore, India.
Fleming
Denise H
DH
Jeyaseelan
Visalakshi
V
Chandy
Sujith J
SJ
Annapandian
V M
VM
Subbanna
P K
PK
John
George T
GT
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000379:methods; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012494:Sampling Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
D007166:Immunosuppressive Agents; D016559:Tacrolimus