Establishing Serum Reference Ranges for Antihypertensive Drugs

Rognstad, Stine; Søraas, Camilla Lund; Bergland, Ola Undrum; Høieggen, Aud; Strømmen, Magnus; Helland, Arne; Opdal, Mimi Stokke

doi:10.1097/ftd.0000000000000806

Cited by 15 publications

(23 citation statements)

References 50 publications

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“…Over the last few years, drug non-adherence has become a leading topic in the field of resistant hypertension (33). Even though witnessed intake virtually guarantees same-day adherence, patients who take a single dose of a drug would be far from reaching a pharmacological steady state, as it requires several half-lives to reach a steady state of serum drug concentration and thus full effect of the drug (34,35). The severe orthostatism experienced by one of the responders during the orthostatic stress test six months after the procedure could be a symptom of simultaneous intake of several antihypertensive drugs that might otherwise not be taken so regularly.…”

Section: Medicationmentioning

confidence: 99%

Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study

et al. 2021

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Purpose: Sympathetic nervous system (SNS) over-activity is associated with essential hypertension.Renal sympathetic denervation (RDN) possibly lowers office-and ambulatory blood pressure (BP) in patients with treatment-resistant hypertension (TRH). We aimed to assess the effect of RDN compared to drug adjustment on SNS activity among patients with TRH by measuring plasma catecholamines and heart rate variability (HRV) during stress tests. Materials and methods:Patients with TRH were randomized to RDN (n=9) or Drug Adjustment (DA) (n=10). We measured continuous HRV and beat-to-beat-BP using FinaPres® and obtained plasma catecholamines during standardized orthostatic-and cold-pressor stress tests (CPT) before-and six months after randomization.Results: CPT revealed no differences between groups at baseline in peak adrenaline concentration (69.3pg/mL in the DA group vs. 70.0pg/mL in the RDN group, p=0.38) or adrenaline reactivity (∆23.1pg/mL in the DA group vs. ∆29.3pg/mL in the RDN group, p=0.40). After six months, adrenaline concentrations were statistically different between groups after one minute (66.9pg/mL in the DA group vs. 55.3pg/mL in the RDN group, p=0.03), and six minutes (62.4pg/mL in the DA group vs. 50.1pg/mL in the RDN group, p=0.03). There was a tendency of reduction in adrenaline reactivity after six months in the RDN group (∆26.3pg/mL at baseline vs. ∆12.8pg/ml after six months, p=0.08), while it increased in the DA group (∆13.6pg/mL at baseline vs. ∆19.9pg/mL after six months, p=0.53).We also found a difference in the Low Frequency band at baseline following the CPT (667µs 2 in the DA group vs. 1628µs 2 in the RDN group, p=0.03) with a clear tendency of reduction in the RDN group to 743µs 2 after six months (p=0.07), compared to no change in the DA group (1052µs 2, p=0.39). Conclusion:Our data suggest that RDN reduces SNS activity after six months. This finding warrants investigation in a larger study.

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Section: Medicationmentioning

confidence: 99%

Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study

et al. 2021

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“…However, methods for urine analysis are mostly qualitative in nature and may lead to overestimation of adherence due to excretion of drugs exceeding the dosing interval manyfold [38]. The assessment of adherence based on blood, serum, or plasma drug concentrations is expected to be more accurate, particularly if a DRC approach is used [12,38,42]. Therefore, this study aimed to close an analytical gap to allow assessing adherence of the most frequently prescribed classes of AHD using just one VAMS tip [6,[27][28][29].…”

Section: Resultsmentioning

confidence: 99%

“…EDTA-stabilized blood was centrifuged for 5 min at 1645 × g to generate plasma. For the assessment of adherence, cut-off concentrations were determined using DRC-factors calculated for the corresponding dosing interval of medication [12,38]. Since most subjects took their medication in the morning and samples were taken about noon, the DRC-factor for ∆t = 6h (∆t = interval between drug intake and blood sampling) was calculated and used for the calculation of cut-off concentrations for the adherence assessment (see ESM equation S1 and Table S4).…”

Section: Proof Of Conceptmentioning

confidence: 99%

“…A limitation of this method is that it is a theoretical calculation based on pharmacokinetic properties of different drugs. Therefore, cut-off concentrations should be clinically validated against measured drug concentrations in patients known to be adherend since pharmacokinetics are influenced by e.g., age, comorbidity, and renal clearance [12]. Additionally, different properties of whole blood and plasma are not considered in this equation.…”

Section: Proof Of Conceptmentioning

confidence: 99%

“…A study by Gupta et al demonstrated that liquid chromatography-mass spectrometry (LC-MS)-based analyses of urine or blood of non-adherent patients improve their adherence with consecutive meaningful reductions in blood pressure [10]. 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.…”

Section: Introductionmentioning

confidence: 99%

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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

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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

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Gender Differences in Cardiac Organ Damage in Arterial Hypertension: Assessing the Role of Drug Nonadherence

Aune,

Ohldieck,

Halvorsen

et al. 2024

High Blood Press Cardiovasc Prev

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Introduction Cardiac organ damage like left ventricular (LV) hypertrophy and left atrial (LA) enlargement is more prevalent in women than men with hypertension, but the mechanisms underlying this gender difference remain unclear. Methods We tested the association of drug nonadherence with the presence of LV hypertrophy and LA enlargement by echocardiography in 186 women and 337 men with uncontrolled hypertension defined as daytime systolic blood pressure (BP) ≥ 135mmHg despite the prescription of at least two antihypertensive drugs. Drug adherence was assessed by measurements of serum drug concentrations interpreted by an experienced pharmacologist. Aldosterone-renin-ratio (ARR) was measured on actual medication. Results Women had a higher prevalence of LV hypertrophy (46% vs. 33%) and LA enlargement (79% vs 65%, both p < 0.05) than men, while drug nonadherence (8% vs. 9%, p > 0.514) did not differ. Women were older and had lower serum renin concentration and higher ARR than men, while 24-h systolic BP (141 ± 9 mmHg vs. 142 ± 9 mmHg), and the prevalences of obesity (43% vs. 50%) did not differ (all p > 0.10). In multivariable analyses, female gender was independently associated with a two-fold increased risk of LV hypertrophy (OR 2.01[95% CI 1.30–3.10], p = 0.002) and LA enlargement (OR 1.90 [95% CI 1.17–3.10], p = 0.010), while no association with drug nonadherence was found. Higher ARR was independently associated with LV hypertrophy in men only (OR 2.12 [95% CI 1.12–4.00] p = 0.02). Conclusions Among patients with uncontrolled hypertension , the higher prevalence of LV hypertrophy and LA enlargement in women was not explained by differences in drug nonadherence. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03209154. Supplementary Information The online version contains supplementary material available at 10.1007/s40292-024-00632-6.

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Establishing Serum Reference Ranges for Antihypertensive Drugs

Cited by 15 publications

References 50 publications

Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study

Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study

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

Gender Differences in Cardiac Organ Damage in Arterial Hypertension: Assessing the Role of Drug Nonadherence

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