Institute of Legal Medicine, Department of Forensic Toxicology, University Hospital, Goethe University, Frankfurt/Main, Germany.
Department of Nephrology, Medical Clinic III, University Hospital, Goethe University, Frankfurt/Main, Germany.
PLoS One. 2020 Aug 10;15(8):e0237383. doi: 10.1371/journal.pone.0237383. eCollection 2020.
With obesity having doubled in the last decade, hypertension is on the rise. In one-third of hypertensive patients the metabolic syndrome is present. This might be one factor for the increasing number of prescriptions for angiotensin receptor blockers and calcium-channel blockers besides a more favorable risk-to-benefit ratio. The aim of the present study was to evaluate a therapeutic drug monitoring (TDM) method for assessment of adherence based on cut-offs in inpatients and to compare it to an established urine drug screening in outpatients. A method for quantification of calcium-channel blockers and angiotensin receptor blockers using high-performance liquid chromatography-tandem mass spectrometric analysis (LC-MS/MS) was developed and validated. The method was applied to serum samples of 32 patients under supervised medication to establish cut-off values for adherence assessment based on dose-related concentrations (DRC, calculated from pharmacokinetic data). Furthermore, corresponding urine and blood samples of 42 outpatients without supervised medication were analysed and the results compared with regard to adherence assessment. All serum concentrations measured for amlodipine (n = 40), lercanidipine (n = 14), candesartan (n = 10), telmisartan (n = 4) and valsartan (n = 10) in inpatients were above the patient specific lower DRC confirming adherence. Of 42 outpatients the identification of analytes in urine as well as the quantification in serum exhibited differing results. According to urinalysis, adherence was demonstrated in only 87.0% of prescriptions, compared to 91.3% for serum analyses. Differences were observed for amlodipine, lercanidipine and candesartan which can be explained by a higher specificity of the serum analysis approach due to pharmacokinetics. The present study confirms that assessing adherence based on serum drug concentrations with individually calculated lower DRCs is more accurate than using qualitative urine analysis. In particular, drugs with low bioavailability, low renal excretion or high metabolism rate such as lercanidipine and candesartan may lead to underestimation of adherence via urine analysis.
由于过去十年肥胖症的发病率翻了一番，高血压的发病率也在上升。三分之一的高血压患者存在代谢综合征。这可能是血管紧张素受体阻滞剂和钙通道阻滞剂处方数量增加的一个因素，此外，这些药物的风险收益比也更有利。本研究的目的是评估一种基于住院患者的药物浓度监测（TDM）方法来评估药物依从性，并将其与已建立的门诊尿液药物筛查方法进行比较。建立了一种使用高效液相色谱-串联质谱分析（LC-MS/MS）定量钙通道阻滞剂和血管紧张素受体阻滞剂的方法，并对其进行了验证。该方法应用于 32 名接受监督用药的患者的血清样本中，根据与剂量相关的浓度（DRC，根据药代动力学数据计算得出）建立药物依从性评估的截止值。此外，还分析了 42 名未接受监督用药的门诊患者的相应尿液和血液样本，并比较了评估药物依从性的结果。所有住院患者测量的氨氯地平（n = 40）、乐卡地平（n = 14）、坎地沙坦（n = 10）、替米沙坦（n = 4）和缬沙坦（n = 10）的血清浓度均高于患者特异性的较低 DRC，证实了药物依从性。42 名门诊患者中，尿液样本中分析物的鉴定和血清样本的定量结果不同。根据尿液分析，药物依从性仅在 87.0%的处方中得到证实，而血清分析的依从性为 91.3%。氨氯地平、乐卡地平和坎地沙坦的结果存在差异，这可以用血清分析方法由于药代动力学而具有更高的特异性来解释。本研究证实，基于个体计算的较低 DRC 的血清药物浓度评估药物依从性比使用定性尿液分析更准确。特别是对于生物利用度低、肾排泄率低或代谢率高的药物，如乐卡地平利坎地沙坦，通过尿液分析可能会低估药物依从性。
