Willis C, Taylor P J, Salm P, Tett S E, Pillans P I
School of Pharmacy, University of Queensland, St. Lucia, Brisbane QLD, Australia.
Ther Drug Monit. 2000 Oct;22(5):549-54. doi: 10.1097/00007691-200010000-00008.
Mycophenolate mofetil, the oral prodrug of mycophenolic acid, is indicated as immunosuppressive therapy after renal transplantation. To aid in the investigation of pharmacokinetic-pharmacodynamic relationships of mycophenolic acid in the clinical setting, limited blood sampling strategies have been proposed, and models from these developed, for the estimation of mycophenolic acid area under the concentration-time curve (AUC). In the current study, the authors investigated the predictive performance of six published models to estimate AUC. A total of 49 profiles from 25 renal transplant patients were used to test each model's performance against a full 14 time-point AUC. A wide range of agreement was found when predicted AUCs were compared with full AUCs using linear regression analysis (range: r2 = 0.499 to 0.836). Model 1, which uses 4 time-points over 6 hours, was found to be superior to all other models. The range of time-points used in this model takes into account patients with variable absorption. This model should be further tested on data sets from other centers. The relatively poor performance of the other models may be caused by their inability to describe the peak concentration in these patients. Caution is warranted when using limited sampling strategies on patients whose absorption of mycophenolic acid is altered, compared with those of the pharmacokinetic profiles from which the model was developed.
霉酚酸酯，即霉酚酸的口服前体药物，被用作肾移植后的免疫抑制治疗。为了有助于在临床环境中研究霉酚酸的药代动力学-药效学关系，人们提出了有限采样策略，并据此开发了模型，用于估算霉酚酸浓度-时间曲线下面积（AUC）。在本研究中，作者调查了六个已发表模型估算AUC的预测性能。共使用了25例肾移植患者的49份血药浓度数据来测试每个模型相对于完整14个时间点AUC的性能。使用线性回归分析将预测的AUC与完整AUC进行比较时，发现一致性范围很广（范围：r2 = 0.499至0.836）。发现使用6小时内4个时间点的模型1优于所有其他模型。该模型中使用的时间点范围考虑了吸收情况各异的患者。该模型应在其他中心的数据集上进一步测试。其他模型相对较差的性能可能是由于它们无法描述这些患者的峰值浓度。与开发该模型所依据的药代动力学数据的患者相比，对霉酚酸吸收发生改变的患者使用有限采样策略时应谨慎。
