Department of Laboratory Medicine, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary.
Department of Internal Medicine and Hematology, Semmelweis University, Szentkirályi út 46, H-1088 Budapest, Hungary.
Molecules. 2021 Mar 2;26(5):1324. doi: 10.3390/molecules26051324.
The antihyerlipidemic drug atorvastatin (ATR) is used worldwide as part of the strategy to prevent cardiovascular events. The high prevalence of patient nonadherence remains an important challenge which could be addressed efficiently by precision pharmacotherapy based on therapeutic drug monitoring (TDM). ATR is metabolized to pharmacologically active metabolites, and evidence shows that the sums of ATR acid and lactone form concentrations (ATR + ATRL), or of ATR and hydroxylated metabolites (ATR + MET) should be assayed. A method is presented for the analysis of these substances in serum. Method validation included the estimation of the quantitative relationship between the concentrations and the standard deviations (SD), which supports the optimal incorporation of TDM results into nonparametric pharmacokinetic models. The concentrations of the analytes were evaluated in human subjects receiving ATR. The method's performance improved by taking the sums of acid and lactone concentrations into account. The concentration-SD relationship was linear, and we recommend applying Theil's regression for estimating the assay error. All analytes could be detected by 2 h post dose in the samples of human subjects. The changes in metabolite/parent drug concentration ratios in time depended on the dose. The method is suitable for the TDM of ATR with a focus on precision pharmacotherapy.
降脂药阿托伐他汀（ATR）在全球范围内被用作预防心血管事件策略的一部分。患者不依从的高患病率仍然是一个重要的挑战，可以通过基于治疗药物监测（TDM）的精准药物治疗来有效解决。ATR 被代谢为具有药理活性的代谢物，有证据表明，ATR 酸和内酯形式浓度的总和（ATR+ATR L）或 ATR 和羟基化代谢物的总和（ATR+MET）应该进行检测。本文提出了一种用于分析这些物质在血清中的方法。方法验证包括估计浓度与标准差（SD）之间的定量关系，这支持将 TDM 结果最佳纳入非参数药代动力学模型。该方法在接受 ATR 治疗的人体受试者中评估了分析物的浓度。通过考虑酸和内酯浓度的总和，提高了方法的性能。浓度-SD 关系呈线性，我们建议应用 Theil 回归估计检测误差。在人体受试者的样本中，所有分析物在给药后 2 小时内均可检测到。代谢物/母体药物浓度比值随时间的变化取决于剂量。该方法适用于以精准药物治疗为重点的 ATR 的 TDM。
