INTRODUCTION: Once-daily extended-release formulation of tacrolimus (QD-TAC) is expected to provide equal effects to the twice-daily formulation of tacrolimus with better drug adherence. As a matter of fact, the pharmacokinetics is quite different between two distinct formulations. Then we examined the predictive performance of limited sampling strategy (LSS) for estimation of tacrolimus exposure in adult kidney transplant recipients under QD-TAC based immunosuppresion.
METHODS: Thirty-six adult kidney recipients (male 22, female 14, mean age 49.1±12.2 ys) who were taking QD-TAC were included. First we calculated half and full area under the concentration-time curve (AUC0-12 and AUC0-24) from their multiple time point blood samples (0 pre-, 0.5, 1, 2, 3, 4, 6, 12, 24hr post-dose) using a trapezoid method. Each concentrations of TAC were measured by an ACMIA. Next we derived a LSS to obtained the predictive formula from 1 to 3 time points by multiple regression analysis using a linear-least squares correlation method.
RESULTS: A single time point analysis revealed that the best correlation were observed using C6 in AUC0-12 (=8.40xC6 + 30.38, r²=0.804) or C12 in AUC0-24 (=22.93xC12 + 27.77, r²=0.880). In 2 time points analysis, C2 and C6 are the most reliable time points in AUC0-12 (=3.21xC2 + 6.73xC6 + 9.01, r²=0.956), while C4 and C12 are in AUC0-24 (=6.03xC4 + 6.96xC12 + 45.22,
r²=0.950). Three time points analysis showed the strongest correlation using C1, C3 and C6 in AUC0-12 (=1.37xC1 + 2.82xC3 + 5.89xC6 + 7.78, r²=0.978) and C3, C6 and C12 in AUC0-24 (=3.88xC3 + 4.94xC6 + 12.37xC12 + 5.45, r²=0.981). Moreover, AUC0-24 has a strong correlation with AUC0-12 (AUC0-12= 0.6098xAUC0-24 + 0.0562, r²= 0.95801) calculated as above. Thus C1, C3 and C6 yield proper AUC0-12 or AUC0-24.
CONCLUSION: TAC exposure in adult kidney recipients on 12 or 24-hourly QD-TAC dosing can be estimated by a limited early time point-based LSS with higher correlation even with 2-3 time points analysis than single time point analysis. We also should consider different sampling time points in calculation AUC0-12 from AUC0-24 with LSS.
To cite this abstract in AMA style:Harada H, Achiwa K, Fukuzawa N, Yuki Y, Hotta K, Seki T, Togashi M. Establishment of Limited Sampling Strategy for the Estimation of Once-Daily Extended-Release Formulation of Tacrolimus Exposure in Adult Kidney Transplant Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/establishment-of-limited-sampling-strategy-for-the-estimation-of-once-daily-extended-release-formulation-of-tacrolimus-exposure-in-adult-kidney-transplant-recipients/. Accessed October 31, 2020.
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