Diamond Adam, Karhadkar Sunil, Chavin Kenneth, Constantinescu Serban, Lau Kwan N, Perez-Leal Oscar, Mohrien Kerry, Sifontis Nicole, Di Carlo Antonio
Department of Pharmacy, Temple University Hospital, Philadelphia, PA 19140, United States.
Department of Surgery, Temple University Hospital, Philadelphia, PA 19140, United States.
World J Transplant. 2023 Dec 18;13(6):368-378. doi: 10.5500/wjt.v13.i6.368.
Tacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on expression. Patients who express often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the setting.
To obtain target trough concentrations of extended-release tacrolimus in kidney transplant recipients according to genotype.
Single-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of genotype was performed at study conclusion.
Mean time to therapeutic tacrolimus trough concentration was longer in intermediate and extensive metabolizers non-expressers (6 d 13.5 d 4.5 d; = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in intermediate and extensive metabolizers non-expressers (16 mg 16 mg 12 mg; = 0.010) (0.20 mg/kg 0.19 mg/kg 0.13 mg/kg; = 0.018). extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to intermediate metabolizers and non-expressers (7.98 ng/mL 9.18 ng/mL 10.78 ng/mL; = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients.
Expression of leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for expressers.
他克莫司缓释片已获美国食品药品监督管理局批准用于肾移植人群。他克莫司的给药要求通常因多种因素而异，包括基于表达的代谢差异。表达的患者通常需要更高剂量的即释型他克莫司，但在这种情况下，他克莫司缓释片尚未得到证实。
根据基因型在肾移植受者中获得他克莫司缓释片的目标谷浓度。
单臂、前瞻性、单中心、开放标签、观察性研究（ClinicalTrials.gov：NCT03713645）。根据实际体重，以0.13mg/kg/天的起始剂量每日口服一次生命周期制药他克莫司（LCPT）。如果体重超过理想体重的120%，则使用调整后的体重。调整LCPT剂量以维持他克莫司谷浓度在8-10ng/mL。在研究结束时对基因型进行药物遗传学分析。
中间代谢型和广泛代谢型非表达者达到治疗性他克莫司谷浓度的平均时间比非表达者更长（6天对13.5天对4.5天；P=0.025）。中间代谢型和广泛代谢型非表达者达到治疗浓度的平均他克莫司剂量和基于体重的剂量更高（16mg对16mg对12mg；P=0.010）（0.20mg/kg对0.19mg/kg对0.13mg/kg；P=0.018）。在整个研究期间，广泛代谢型患者的平均他克莫司谷浓度低于中间代谢型和非表达者（7.98ng/mL对9.18ng/mL对10.78ng/mL；P=0对0.008）。移植后30天时，肾移植功能方面未发现差异。13名（36%）患者报告了严重不良事件。
的表达导致更高的起始剂量和递增剂量滴定他克莫司缓释片以达到目标谷浓度。我们建议表达者的起始剂量为0.2mg/kg/d。
