Pharmacology and Transplantation, INSERM U1248, Université de Limoges ; and.
Department of Pharmacology, Toxicology and Pharmacovigilance, CHU de Limoges, Limoges, France.
Ther Drug Monit. 2023 Oct 1;45(5):591-598. doi: 10.1097/FTD.0000000000001087. Epub 2023 Feb 22.
The Immunosuppressant Bayesian Dose Adjustment web site aids clinicians and pharmacologists involved in the care of transplant recipients; it proposes dose adjustments based on the estimated area under the concentration-time curve (AUCs). Three concentrations (T 20 min , T 1 h , and T 3 h ) are sufficient to estimate mycophenolic acid (MPA) AUC 0-12 h in pediatric kidney transplant recipients. This study investigates mycophenolate mofetil (MMF) doses and MPA AUC values in pediatric kidney transplant recipients, and target exposure attainment when the proposed doses were followed, through a large-scale analysis of the data set collated since the inception of the Immunosuppressant Bayesian Dose Adjustment web site.
In this study, 4051 MMF dose adjustment requests, corresponding to 1051 patients aged 0-18 years, were retrospectively analyzed. AUC calculations were performed in the back office of the Immunosuppressant Bayesian Dose Adjustment using published Bayesian and population pharmacokinetic models.
The first AUC request was posted >12 months posttransplantation for 41% of patients. Overall, only 50% had the first MPA AUC 0-12 h within the recommended 30-60 mg.h/L range. When the proposed dose was not followed, the proportion of patients with an AUC in the therapeutic range for MMF with cyclosporine or tacrolimus at the subsequent request was lower (40% and 45%, respectively) than when it was followed (58% and 60%, respectively): P = 0.08 and 0.006, respectively. Furthermore, 3 months posttransplantation, the dispersion of AUC values was often lower at the second visit when the proposed doses were followed, namely, P = 0.03, 0.003, and 0.07 in the 4 months-1 year, and beyond 1 year with <6-month or >6-month periods between both visits, respectively.
Owing to extreme interindividual variability in MPA exposure, MMF dose adjustment is necessary; it is efficient at reducing such variability when based on MPA AUC.
免疫抑制剂贝叶斯剂量调整网站辅助参与移植受者护理的临床医生和药理学家；它基于估计的浓度-时间曲线下面积（AUC）来提出剂量调整建议。在儿科肾移植受者中，仅需 3 个浓度（T 20 分钟、T 1 小时和 T 3 小时）即可估计麦考酚酸（MPA）AUC 0-12 小时。本研究通过对免疫抑制剂贝叶斯剂量调整网站成立以来收集的数据进行大规模分析，调查了儿科肾移植受者中美法莫替丁（MMF）剂量和 MPA AUC 值，以及在遵循建议剂量时的目标暴露度。
在这项研究中，回顾性分析了 4051 次 MMF 剂量调整请求，对应于 1051 名 0-18 岁的患者。AUC 计算在免疫抑制剂贝叶斯剂量调整的后台进行，使用已发表的贝叶斯和群体药代动力学模型。
41%的患者在移植后>12 个月时首次提出 AUC 请求。总体而言，只有 50%的患者首次 MPA AUC 0-12 小时在推荐的 30-60mg.h/L 范围内。当未遵循建议剂量时，在随后的请求中，与遵循建议剂量相比，环孢素或他克莫司时具有治疗范围内 MMF 和 MPA AUC 的患者比例较低（分别为 40%和 45%）：P=0.08 和 0.006。此外，在移植后 3 个月，当遵循建议剂量时，在第二次就诊时 AUC 值的离散度通常较低，即分别在 4 个月-1 年和 1 年以上、两次就诊之间的时间间隔为<6 个月或>6 个月时，P=0.03、0.003 和 0.07。
由于 MPA 暴露的个体间差异很大，因此需要调整 MMF 剂量；当基于 MPA AUC 进行调整时，它可以有效地降低这种变异性。
