Baccarani Umberto, Velkoski Jaqueline, Pravisani Riccardo, Adani Gian Luigi, Lorenzin Dario, Cherchi Vittorio, Falzone Bruno, Baraldo Massimo, Risaliti Andrea
Clinica Chirurgica, Centro Trapianti di Fegato-Rene - Dipartimento di Area Medica. Università di Udine, Udine, Italy.
Clinica Chirurgica, Centro Trapianti di Fegato-Rene - Dipartimento di Area Medica. Università di Udine, Udine, Italy.
Transplant Proc. 2019 Nov;51(9):2971-2973. doi: 10.1016/j.transproceed.2019.03.084. Epub 2019 Oct 10.
An extended-release formulation of tacrolimus designed for once-daily administration (LCP-TAC) is a new prolonged-release tacrolimus (TAC-PR) formulation using a drug delivery technology designed to enhance the bioavailability of drugs compared with TAC-PR. The aim of this study was to retrospectively compare de novo administration of LCP-TAC and TAC-PR for therapeutic trough levels and daily dosage during the first 30 days after first liver transplant (LT).
A total of 35 patients submitted to first LT between 2016 and 2018 were retrospectively enrolled: 16 received LCP-TAC, while 19 received TAC-PR as de novo immunosuppression. Patients were analyzed for daily dosage and trough levels at postoperative days (PODs) 3, 7, 15, and 30.
The initial dose of tacrolimus did not differ between LCP-TAC and TAC-PR (mean, 5.19 [SD, 1.72] mg/d vs mean, 5.26 [SD, 1.91] mg/d, P = .90). On PODs 7, 15, and 30 the daily dosage was statistically lower for LCP-TAC compared with TAC-PR (mean, 5.44 [SD, 2.06] mg/d vs mean, 7.68 [SD, 2.91] mg/d, P = .01; mean, 5.33 [SD, 2.23] mg/d vs mean, 8.82 [SD, 2.35] mg/d, P < .001; and mean, 5.38 [SD, 2.50] mg/d vs mean, 9.81 [SD, 3.78] mg/d, P < .001, respectively). The therapeutic trough levels were significantly higher for LCP-TAC on POD 3 (mean, 5.05 [SD, 3.58] ng/mL vs mean, 2.42 [SD, 2.75] ng/mL, P = .03) and POD 5 (mean, 7.35 [SD, 5.12] ng/mL vs mean, 4.17 [SD, 2.05] ng/mL, P = .04), while no differences were found on PODs 7, 15, and 30.The percentage of patients on POD 3 achieving a trough level higher than 6 ng/mL was higher for LCP-TAC than TAC-PR (40% vs 13%, P = .05).
LCP-TAC after LT is safe and might enhance bioavailability, reducing the amount of drug necessary to achieve therapeutic trough levels compared with TAC-PR.
他克莫司缓释制剂设计为每日一次给药（LCP-TAC），是一种新型的延长释放他克莫司（TAC-PR）制剂，采用了一种药物递送技术，旨在与TAC-PR相比提高药物的生物利用度。本研究的目的是回顾性比较首次肝移植（LT）后前30天LCP-TAC和TAC-PR的初始给药的治疗谷浓度和每日剂量。
回顾性纳入2016年至2018年间接受首次LT的35例患者：16例接受LCP-TAC，19例接受TAC-PR作为初始免疫抑制治疗。分析患者术后第3、7、15和30天的每日剂量和谷浓度。
LCP-TAC和TAC-PR的他克莫司初始剂量无差异（均值分别为5.19[标准差，1.72]mg/d和5.26[标准差，1.91]mg/d，P = 0.90）。在术后第7、15和30天，LCP-TAC的每日剂量在统计学上低于TAC-PR（均值分别为5.44[标准差，2.06]mg/d和7.68[标准差，2.91]mg/d，P = 0.01；均值分别为5.33[标准差，2.23]mg/d和8.82[标准差，2.35]mg/d，P < 0.001；均值分别为5.38[标准差，2.50]mg/d和9.81[标准差，3.78]mg/d，P < 0.001）。LCP-TAC在术后第3天（均值分别为5.05[标准差，3.58]ng/mL和2.42[标准差，2.75]ng/mL，P = 0.03）和第5天（均值分别为7.35[标准差，5.12]ng/mL和4.17[标准差，2.05]ng/mL，P = 0.04）的治疗谷浓度显著高于TAC-PR，而在术后第7、15和30天未发现差异。LCP-TAC术后第3天谷浓度高于6 ng/mL的患者百分比高于TAC-PR（40%对13%，P = 0.05）。
LT后使用LCP-TAC是安全的，可能会提高生物利用度，与TAC-PR相比，达到治疗谷浓度所需的药物量减少。
