A Steady-State Head-to-Head Pharmacokinetic Comparison of All FK-506 (Tacrolimus) Formulations (ASTCOFF): An Open-Label, Prospective, Randomized, Two-Arm, Three-Period Crossover Study

详细信息    查看全文

• 作者：S. Tremblay ; V. Nigro ; J. Weinberg ; E. S. Woodle and R. R. Alloway
• 刊名：American Journal of Transplantation
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：17
• 期：2
• 页码：432-442
• 全文大小：415K
• ISSN：1600-6143

文摘

This two-sequence, three-period crossover study is the first pharmacokinetic (PK) study to compare all three innovator formulations of tacrolimus (twice-daily immediate-release tacrolimus capsules [IR-Tac]; once-daily extended-release tacrolimus capsules [ER-Tac]; novel once-daily tacrolimus tablets [LCPT]). Stable renal transplant patients were dosed with each drug for 7 days, and blood samples were obtained over 24 h. Thirty subjects were included in the PK analysis set. A conversion factor of 1:1:0.80 for IR-Tac:ER-Tac:LCPT was used; no dose adjustments were permitted during the study. The median (interquartile range) total daily dose was 6.0 (4.0–8.0) mg for IR-Tac and ER-Tac and 4.8 (3.3–6.3) for LCPT. Significantly higher exposure on a per milligram basis, lower intraday fluctuation and prolonged time (T_max) to peak concentration (C_max) were found for LCPT versus IR-Tac or ER-Tac. ER-Tac showed no differences versus IR-Tac in exposure, C_max, T_max or fluctuation. The observed exposure of IR-Tac was used to normalize exposure for LCPT and ER-Tac, resulting in the following recommended total daily dose conversion rates: IR-Tac:ER-Tac, +8%; IR-Tac:LCPT, −30%; ER-Tac:LCPT, −36%. After exposure normalization, C_max was ~17% lower for LCPT than for IR-Tac or ER-Tac; C_min was ~6% lower for LCPT compared with IR-Tac and 3% higher compared with ER-Tac.