Assessing Adherence to Antihypertensive Medication by Means of Dose-Dependent Reference Plasma Concentration Ranges and Ultra-High Performance Liquid Chromatography-Ion Trap Mass Spectrometry Analysis

Wagmann, Lea; Vollmer, Aline C.; Lauder, Lucas; Mahfoud, Felix; Meyer, Markus R.

doi:10.3390/molecules26051495

Cited by 8 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In terms of clinical application, analysis of drug concentrations in blood serum is useful in detecting patient nonadherence to antihypertensive medication. Many recent studies found high rates of non-adherence to antihypertensive therapies which prompt simple and reliable monitoring of medication adherence with special attention to at-risk groups of patients [ 28 , 29 , 30 , 31 , 32 ]. Meantime, AML is the perfect first-line medicine available in a single fixed-dose combination form for different cardiovascular diseases with excellent pharmacokinetic parameters [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Opportunities of Amlodipine as a Potential Candidate in the Evaluation of Drug Compliance during Antihypertensive Therapy

et al. 2023

View full text Add to dashboard Cite

Background and Objectives: Blood pressure measurement is essential evidence to establish that the chosen medicine and dosage are appropriate, and also indirectly indicates whether the medicine is being used at all. Therefore, current research compares adherence to the target blood pressure at home and in the hospital between different age groups, using similar combinations of the drugs prescribed by the doctor within ongoing antihypertensive therapy. Moreover, it is very important to develop a method for the determination of amlodipine and its metabolite, which would suitable for clinical applications, when the result is needed as quick as possible. Materials and Methods: This prospective study included patients aged ≥18 years who were diagnosed with hypertension. Subjects were divided into two age groups according to European Society of Cardiology (ESC) hypertension guidelines; older patients (≥65 years) and adult patients (<65 years). Assessment of adherence rate to antihypertensive medications was performed using a measurement of systolic blood pressure and comparing this to ESC hypertension guideline data. A simple liquid chromatography-tandem mass spectrometer (LC-MS/MS) method for determination of amlodipine and dehydroamlodipine was developed and validated according to the European Medicines Agency guideline on bioanalytical method validation at the Latvian Institute of Organic Synthesis. Results: A total of 81 patients with arterial hypertension were enrolled in this study. A significant number of patients were overweight (N = 33, 40.7%) and obese (N = 36, 44.4%). To control arterial hypertension, 70 (86.4%) patients used fixed-dose combinations, where one of the components was amlodipine. Practically, 36 (44.4%) hypertensive subjects were not able to comply with target blood pressure. Nonetheless, 38 (46.9%) patients who received fixed-dose combinations were able to comply with target blood pressure. Conclusions: Adherence to ESC hypertension guideline proposed target blood pressure was relatively low among hypertensive subjects even though a significant number of patients were taking fixed-dose combinations. Therefore, optimizing prevention, recognition, and care of hypertensive young adults require intensive educational interventions. Moreover, survey data suggest that therapeutic drug monitoring using the validated simple, sensitive LC-MS/MS method is pivotal for further understanding factors influencing adherence.

show abstract

Section: Discussionmentioning

confidence: 99%

Opportunities of Amlodipine as a Potential Candidate in the Evaluation of Drug Compliance during Antihypertensive Therapy

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Измерение концентрации ЛС в крови является перспективным практическим подходом в оценке комплаенса и адаптации доз и схем лечения для отдельных пациентов. Высокоэффективная жидкостная хроматография с масс-спектрометрией (ВЭЖХ/МС) -это объективный высокоточный и широко используемый метод терапевтического мониторинга лекарственных препаратов, который привлек внимание исследователей к оценке приверженности лечению у пациентов с высоким сердечно-сосудистым риском [8][9][10].…”

Section: терапевтический лекарственный мониторинг для оценки комплаен...unclassified

“…Пациенты с уровнями сывороточной концентрации по крайней мере 1 прописанного АГП ниже минимального предела обнаружения считаются неприверженными лечению. Именно такой методологический подход используется для оценки приверженности пациентов с АГ антигипертензивной терапии [10]. Разработка таких методик в исследовании на небольшой выборке пациентов с АГ (n=91) показала, что при качественном анализе (положительные/отрицательные) доля неприверженных составляла 6,6%, тогда как использование количественного анализа до пороговых значений концентраций позволяет более точно выявлять долю неприверженных пациентов до 19,8% [9].…”

Section: терапевтический лекарственный мониторинг для оценки комплаен...unclassified

“…https://doi.org/10.26442/20751753.2022. 10.201872 REVIEW резистентной гипертензии и высокого экономического бремени для здравоохранения. Важность оптимального контроля АД является одной из главных задач предупреждения сердечно-сосудистых осложнений АГ (инфаркта миокарда, инсульта, почечной недостаточности, смертности) и определяется во всех зарубежных и международных клинических руководствах, при этом частота контролируемой гипертензии среди пациентов с АГ значительно варьирует в популяциях.…”

unclassified

See 1 more Smart Citation

On the issue of low adherence of patients to antihypertensive therapy: the use of therapeutic drug monitoring of drugs: A review

Леонова¹

2022

Consilium Medicum

View full text Add to dashboard Cite

Low adherence of patients to antihypertensive therapy remains an urgent problem and is recognized as the main cause of insufficient BP control at the population level. In this regard, to increase the motivation of patients in clinical practice, methods for assessing adherence (compliance) to drugs. Along with indirect assessment methods (questionnaires, self-reports, pill counts, etc.), which, however, do not always reflect the real patients adherence, more objective is the measurement of antihypertensive drug concentrations in physiological fluids therapeutic drug monitoring (TDM). For these purposes, methods of high-performance liquid chromatography with mass spectrometry were recently adapted, reference ranges of antihypertensive drug concentrations in blood serum and urine for standard doses of drugs were determined, as well as criteria for assessing complete or partial non-compliance. There have been a number of studies using TDM to assess adherence, which show a high rate of non-compliance (low compliance) of more than 50% of cases with a variability from 25 to 86.1%, with complete non-compliance 10.134.5% in patients with uncontrolled and/or resistant hypertension (3 antihypertensive drug). In a population of patients with a normal course of hypertension, taking 12 antihypertensive drug, the level of non-compliance according to the results of TDM did not exceed 10%. Comparison of the TDM method with indirect methods of assessing adherence did not reveal consistency; at the same time, the detection of antihypertensive drug better characterized the clinical problems of patients with arterial hypertension. In clinical practice, direct assessment methods (TDM) can be used to measure adherence in problem patients with uncontrolled hypertension and high cardiovascular risk despite optimal therapy.

show abstract

“…Hereby, assessing adherence based on blood concentrations with individually calculated lower dose-related concentrations (DRC) is more accurate than using qualitative analysis alone [11,12]. Up to date, several LC-MS methods for the quantification of AHD exist [13][14][15][16] but they are based on blood, plasma, or serum needing venipuncture, which can cause discomfort and anxiety and requires healthcare professionals. With dried blood spots (DBS), an alternative to venipuncture is known since 1963 [17].…”

Section: Introductionmentioning

confidence: 99%

Closing the gap — development of an analytical methodology using volumetric absorptive microsampling of finger prick blood followed by LC-HRMS/MS for adherence monitoring of antihypertensive drugs

et al. 2022

Self Cite

View full text Add to dashboard Cite

Volumetric absorptive microsampling (VAMS), an emerging microsampling technique, is a promising tool for adherence monitoring. This study focused on development of an analytical methodology to improve VAMS-based strategies for adherence assessment by analyzing angiotensin-converting-enzyme (ACE) inhibitors, loop diuretics, a potassium-sparing diuretic, and a thiazide diuretic. Development included sample preparation, chromatographic conditions, mass spectrometry settings, validation, and demonstrating proof of concept. Quantification of analytes, by name furosemide, hydrochlorothiazide, lisinopril, torasemide, and the active metabolites, canrenone, enalaprilat, and ramiprilat in finger prick blood (FPB), was validated based on international guidelines. Selectivity, carryover, and within/between-run accuracy and precision were in accordance with the recommendations. The matrix effect was evaluated at three different hematocrit levels (HT: 20%, 40%, 60%) and the coefficients of variation did not exceed 15%. Dilution integrity (1:10 and 1:20) was given for all analytes except lisinopril, yet for lisinopril, the therapeutic range was already covered by the calibration range. Long-term stability in VAMS tips was tested for 2 weeks at 24 °C in the dark and revealed no degradation of analytes. The proof of concept was performed by analyzing 35 intakes of ACE-inhibitors and diuretics in 18 VAMS and matched plasma samples. Hereby, determined concentration in FPB and plasma cannot be used interchangeably, and thus specific reference ranges for whole blood must be established. Nevertheless, the VAMS-based strategy was shown to be suitable for assessing adherence of all classes of antihypertensive drugs used in the guidelines to manage hypertension. Graphical abstract

show abstract

Assessing Adherence to Antihypertensive Medication by Means of Dose-Dependent Reference Plasma Concentration Ranges and Ultra-High Performance Liquid Chromatography-Ion Trap Mass Spectrometry Analysis

Cited by 8 publications

References 38 publications

Opportunities of Amlodipine as a Potential Candidate in the Evaluation of Drug Compliance during Antihypertensive Therapy

Opportunities of Amlodipine as a Potential Candidate in the Evaluation of Drug Compliance during Antihypertensive Therapy

On the issue of low adherence of patients to antihypertensive therapy: the use of therapeutic drug monitoring of drugs: A review

Closing the gap — development of an analytical methodology using volumetric absorptive microsampling of finger prick blood followed by LC-HRMS/MS for adherence monitoring of antihypertensive drugs

Contact Info

Product

Resources

About