Vethe Nils Tore, Husebye Einar, Andersen Anders M, Bergan Stein, Kristiansen Oscar, Fagerland Morten W, Munkhaugen John
Department of Pharmacology, Oslo University Hospital, Oslo.
Department of Medicine, Vestre Viken Trust, Drammen Hospital, Drammen.
Ther Drug Monit. 2022 Aug 1;44(4):558-567. doi: 10.1097/FTD.0000000000000992.
Poor statin adherence remains a public health concern associated with adverse outcomes. We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD).
Eighteen patients with CHD taking an evening dose of simvastatin 20 mg (n = 7), 40 mg (n = 5), or 80 mg (n = 6) were examined at steady-state pharmacokinetics. Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days. Dose-normalized plasma concentrations of simvastatin lactone and simvastatin acid and the sum of the 2 were evaluated to discriminate between adherent dosing and dose omission. Bioanalytical quantification was performed using liquid chromatography-tandem mass spectrometry.
A simvastatin acid cutoff of 1.0 × 10 -2 nmol -1 ·L -1 ·mg -1 identified 100% of those omitting 2 doses and 60% of those omitting a single dose. Simvastatin acid showed superior ability to discriminate dose omission, as well as the best agreement between samples handled at ambient and cool temperatures (median deviation 3.5%; interquartile range -2.5% to 13%). The cutoff for a morning dose schedule, with a similar ability to discriminate, was estimated at 2.0 × 10 -3 nmol -1 ·L -1 ·mg -1 .
The present method discriminated between adherence and reduced adherence to simvastatin therapy in patients with CHD. Sample handling is feasible for routine practice, and the assessment of adherence can be performed by direct measurement of simvastatin acid in a blood sample, according to defined cutoff values. Further studies validating the cutoff value and utility for clinical application are encouraged.
他汀类药物依从性差仍是一个与不良后果相关的公共卫生问题。我们评估了使用药代动力学测量来监测冠心病（CHD）患者对辛伐他汀的依从性。
18例服用辛伐他汀20mg（n = 7）、40mg（n = 5）或80mg（n = 6）晚间剂量的冠心病患者在稳态药代动力学时进行检查。10例患者被指示中断辛伐他汀给药，并在随后3天返回进行血样采集。评估辛伐他汀内酯和辛伐他汀酸的剂量标准化血浆浓度以及两者之和，以区分依从给药和漏服剂量。使用液相色谱 - 串联质谱法进行生物分析定量。
辛伐他汀酸截断值为1.0×10⁻²nmol⁻¹·L⁻¹·mg⁻¹可识别100%漏服2剂的患者和60%漏服1剂的患者。辛伐他汀酸在区分漏服剂量方面表现出卓越能力，并且在常温和低温处理的样本之间一致性最佳（中位偏差3.5%；四分位间距 -2.5%至13%）。具有相似区分能力的早晨给药方案的截断值估计为2.0×10⁻³nmol⁻¹·L⁻¹·mg⁻¹。
本方法可区分冠心病患者对辛伐他汀治疗的依从性和依从性降低情况。样本处理对于常规实践是可行的，并且可以根据定义的截断值通过直接测量血样中的辛伐他汀酸来进行依从性评估。鼓励进一步研究验证截断值及其临床应用的效用。
