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oai:figshare.com:article/33718702 2026-09-14T05:29:28Z category_19 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Discordance between trough concentration and tacrolimus exposure on the day of kidney transplantation: a prospective pharmacokinetic study.docx Hye Eun Kwon (22662313) Jin-Myung Kim (22662310) Youngmin Ko (3333819) Sung Shin (3401819) Young Hoon Kim (554681) Joo Hee Jung (4567987) Chung Hee Baek (11383766) Hyosang Kim (3410366) Hyunwook Kwon (4091746) Pharmacology area under the curve kidney transplantation pharmacokinetics tacrolimus therapeutic drug monitoring trough concentration <p>Tacrolimus trough concentration (C0) serves as a surrogate for drug exposure, but perioperative factors may disrupt this relationship early post-transplantation. We assessed whether the morning trough concentration (C0) on the day of kidney transplantation (POD0) accurately reflects 12-h tacrolimus exposure compared with a relatively stable early reference (POD7). We then derived the POD0 C0 corresponding to the same exposure as the conventional POD7 reference (a C0 of 7–9 ng/mL). We prospectively enrolled 80 de novo kidney transplant recipients receiving immediate-release tacrolimus and performed intensive pharmacokinetic sampling on POD0 (C0, C2, C3, C4, C10) and POD7 (C0, C2, C8). Dose-time-anchored AUC0-12 was calculated using the linear trapezoidal rule. The POD0 C0 corresponding to the POD7 reference AUC0-12 was derived by inverting linear, power, and median quantile regression models. Despite only a modest difference in morning C0 values (POD0 median 7.15 vs. POD7 6.40 ng/mL), the POD0 AUC0-12 was substantially higher than that on POD7 (138.9 vs. 105.4 ng·h/mL, p < 0.001); after adjustment for trough concentration, this difference was attenuated but remained significant (approximately +18% at a matched C0). Additionally, the C0–AUC slope on POD0 was approximately 30% lower than on POD7 (12.0 vs. 17.1 per 1 ng/mL). The POD7 reference AUC (125 [IQR 112–144] ng·h/mL at C0 7–9 ng/mL) corresponded on POD0 to a C0 of approximately 6.8 ng/mL (the robust quantile estimate; 5.5–6.8 ng/mL across the three models). Trough C0 levels underestimated tacrolimus exposure on the day of kidney transplantation. On POD0, a trough of approximately 6–8 ng/mL corresponded to an AUC0-12 at or above this relatively stable early reference. These findings are hypothesis-generating and indicate that troughs need not be driven high early to achieve adequate exposure.</p> 2026-09-14T05:29:28Z Dataset Dataset 10.3389/fphar.2026.1939477.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Discordance_between_trough_concentration_and_tacrolimus_exposure_on_the_day_of_kidney_transplantation_a_prospective_pharmacokinetic_study_docx/33718702 CC BY 4.0