School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Clinical Pharmacology, Department of Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.
Intern Med J. 2019 Jan;49(1):79-83. doi: 10.1111/imj.14043.
Tacrolimus is one of the most widely used liver transplant medications. With the increasing number of obese patients requiring liver transplants, knowledge of the effect of body size affecting post-transplant outcomes, for example drug exposure is increasingly required.
(i) To investigate whether patient body size (i.e. total bodyweight) affects trough plasma concentrations of tacrolimus when a standard mg/kg dosing regimen is used; and (ii) to investigate whether obese patients have different numbers of plasma concentrations outside the therapeutic range compared to non-obese patients in the first months after liver transplant.
Using a transplant database, data tacrolimus concentrations were available for 69 patients. Tacrolimus was initially dosed at a standard 0.1 mg/kg/day after liver transplant, and adjusted to maintain a target trough concentration. Trough blood samples, phenotypic and outcome variables were analysed.
Trough concentrations were similar between obese and non-obese patients (P > 0.05) at each sampling day. At day 7 post-transplant, 85.7% and 79.5% of the observed plasma concentrations were outside the recommended therapeutic range for obese and non-obese patients respectively, at day 30, 52.9% and 57.4%, and at 6 months, 18.7% and 27.5%.
In the first week post-transplant, tacrolimus trough concentrations after standard mg/kg dosing post liver transplant appear to be corrected by total bodyweight. Obese patients have a similar number of trough plasma concentrations outside the therapeutic range compared to non-obese patients.
他克莫司是最广泛使用的肝移植药物之一。随着需要肝移植的肥胖患者数量不断增加,人们越来越需要了解体型大小对移植后结局的影响,例如药物暴露情况。
(i)研究在使用标准毫克/千克剂量方案时,患者体型(即总体重)是否会影响他克莫司的谷血浆浓度;(ii)研究肥胖患者与非肥胖患者在肝移植后第一个月内,治疗范围外的血浆浓度数量是否不同。
使用移植数据库,可获得 69 例患者的他克莫司浓度数据。肝移植后,他克莫司最初以标准 0.1 毫克/千克/天的剂量给药,并进行调整以维持目标谷浓度。分析谷血样、表型和结局变量。
在每个采样日,肥胖患者和非肥胖患者的谷浓度相似(P > 0.05)。移植后第 7 天,分别有 85.7%和 79.5%的观察到的血浆浓度超出肥胖和非肥胖患者推荐的治疗范围,第 30 天分别为 52.9%和 57.4%,第 6 个月分别为 18.7%和 27.5%。
在肝移植后标准毫克/千克剂量方案的第一周,他克莫司谷浓度似乎通过总体重进行了校正。肥胖患者与非肥胖患者相比,治疗范围外的谷血浆浓度数量相似。