Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities.
Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities.
复制标题
DOI：
10.1111/cts.13495
复制
发表时间：
2023-05
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
他克莫司（TAC）和霉酚酸（MPA）提供维持免疫抑制，并在老年肾移植受者（KTR）中凭经验给药，导致健康不公平。与成人年龄相比，免疫抑制药代动力学有限。该次要分析比较了年轻、中年和老年黑人和白色KTR中TAC和MPA的药代动力学和不良反应（AE）。在67例移植后≥ 6个月的稳定KTR中进行了12小时TAC和MPA药代动力学和AE评价。调整TAC方案至目标谷值。根据临床反应调整MPA方案。受试者为：年轻人：小于或等于40岁;中年人：大于40至60岁;老年人大于60岁。非房室药代动力学分析确定了0-12 h浓度-时间曲线下面积（AUC 0 - 12 h）、清除率（CL）和CL/体重指数（BMI）（0-h谷值）。测定MPA肝肠再循环（EHR）、MPA-AUC 6 - 12 h/MPA-AUC 0 - 12 h和MPA葡糖苷酸（MPAG）-AUC 0 - 12 h/MPA-AUC 0 - 12 h。使用SAS 9.4版进行单变量方差分析（ANOVA）。估计的肾小球滤过率、MPA和TAC剂量无组间差异。老年人EHR降低，MPA-AUC 6 - 12 h/MPA-AUC 0 - 12 h降低（p = 0.049），MPAG-AUC 0 - 12 h/MPA-AUC 0 - 12 h升高（p = 0.036）。老年人的MPA谷值（p = 0.045）降低。老年人的TAC CL/BMI（p = 0.043）降低。对于治疗性MPA AUC 0 - 12 h：30-60 mg·h/L，34.3%的KTR达到了该目标，55.2%高于治疗范围。77.6%的KTR在TAC AUC 0 - 12 h目标范围内：100-190 ng·h/mL，19.4%低于该范围，无年龄关系。在44%的年轻受试者、26%的中年受试者和7.8%的老年受试者中，两种药物均达到目标AUC 0 - 12 h（p = 0.036）。神经系统AE在老年人中表现出来（p = 0.014）。免疫抑制药代动力学表现出年龄相关差异，老年人中TAC CL/BMI和MPA EHR降低，神经系统AE增加。这种免疫抑制方案可能需要年龄调整的个体化，以优化同种异体移植物功能。
Tacrolimus (TAC) and mycophenolic acid (MPA) provide maintenance immunosuppression and is dosed empirically in elderly kidney transplant recipients (KTRs) resulting in health inequities. Limited immunosuppressive pharmacokinetics are available comparing adult ages. This secondary analysis compared TAC and MPA pharmacokinetics and adverse effects (AEs) among young, middle‐aged, and elderly Black and White KTRs. The 12‐h TAC and MPA pharmacokinetics with AE evaluation were conducted in 67 stable KTRs greater than or equal to 6 months post‐transplant. TAC regimens were adjusted to target troughs. MPA regimens were adjusted using clinical response. Participants were: young: less than or equal to 40 years; middle age: greater than 40 to 60 years, and elderly greater than 60 years. Noncompartmental pharmacokinetic analysis determined area under the concentration‐time curve 0–12 h (AUC0‐12h), clearance (CL), and CL/body mass index (BMI) with 0‐h troughs. MPA enterohepatic recirculation (EHR), MPA‐AUC6‐12h/MPA‐AUC0‐12h, and MPA glucuronide (MPAG)‐AUC0‐12h/MPA‐AUC0‐12h were determined. Univariate analysis of variance (ANOVA) was conducted using SAS version 9.4. No group differences were noted for estimated glomerular filtration rate, MPA, and TAC doses. EHR was reduced in elderly with decreased MPA‐AUC6‐12h/MPA‐AUC0‐12h (p = 0.049) and increased MPAG‐AUC0‐12h/MPA‐AUC0‐12h (p = 0.036). MPA troughs (p = 0.045) were reduced in the elderly. TAC CL/BMI (p = 0.043) was reduced in the elderly. For therapeutic MPA AUC0‐12h: 30–60 mg·h/L, 34.3% KTRs achieved this target with 55.2% greater than the therapeutic range. 77.6% KTR were in the TAC AUC0‐12h target: 100–190 ng·h/mL and 19.4% were below this range with no age relationship. In 44% young, 26% middle‐age and 7.8% elderly subjects achieved target AUC0‐12h for both medications (p = 0.036). Neurologic AEs were manifested in the elderly (p = 0.014). Immunosuppressive pharmacokinetics demonstrated age‐related differences with reduced TAC CL/BMI and MPA EHR and increased neurologic AE in the elderly. This immunosuppressive regimen may require age‐adjusted individualization to optimize allograft function.
登录
查看更多内容
影响因子：
2.9
作者：
Campagne O;Mager DE;Tornatore KM
通讯作者：
Tornatore KM
影响因子：
8.8
作者：
Hart, A.;Lentine, K. L.;Snyder, J. J.
通讯作者：
Snyder, J. J.
影响因子：
4.5
作者：
Tornatore, Kathleen M.;Meaney, Calvin J.;Wilding, Gregory E.;Chang, Shirley S.;Gundroo, Aijaz;Cooper, Louise M.;Gray, Vanessa;Shin, Karen;Fetterly, Gerald J.;Prey, Joshua;Clark, Kimberly;Venuto, Rocco C.
通讯作者：
Venuto, Rocco C.
影响因子：
6.2
作者：
Krenzien F;ElKhal A;Quante M;Rodriguez Cetina Biefer H;Hirofumi U;Gabardi S;Tullius SG
通讯作者：
Tullius SG
影响因子：
4.1
作者：
通讯作者：
--