amlodipine besilate + irbesartan (DSP8153)

Determination of five antihypertensives in dried capillary plasma spots by LC-MS/MS: A novel method for monitoring pharmacotherapy adherence.

Oliveira Debora Renata Macali DRM, Fischer Costa Fernanda F, Duarte Juliana Henrique JH, Roieski Eduarda E et al.

Adherence to hypertension treatment is crucial for therapeutic success, as noncompliance adversely affects quality of life and healthcare costs. Assessing adherence directly through plasma drug concentrations is particularly effective for patients with complex medication regimens. This study aimed to develop and validate an LC-MS/MS method for quantifying five antihypertensive drugs in dried capillary plasma obtained via a plasma separation device. The process involved incubating three 6 mm discs in 150 µL of 0.1% bovine serum albumin, followed by chloride analysis of a 20 µL aliquot after 45 min. The residual volume was precipitated using 25% trichloroacetic acid, then mixed with 500 µL methanol containing internal standards (losartan-D4 and atenolol-D7). The extract was dried, reconstituted with methanol, and combined with the supernatant from protein precipitation for analysis. An octadecylsilic column and gradient elution with 0.1% formic acid in water and acetonitrile were used, with positive electrospray ionization except for hydrochlorothiazide. The analytical run time was eight minutes, exhibiting linear ranges from 0.5 to 200 ng/mL for amlodipine and losartan and 5-2000 ng/mL for atenolol, hydrochlorothiazide, and losartan, with r² > 0.99 and 1/x weighting. Precision and accuracy were acceptable, with CV% ranging from 4.3% to 14.5% and accuracy from 86% to 112%, while extraction yields were between 75% and 101%. The analytes were stable at 23 ºC for 21 days in DPS samples. Comparison of drug concentrations in DPS and fresh plasma samples from 72 patients demonstrated high correlation (r = 0.93-0.98), indicating reliability in assessing therapy adherence. Lower concentrations of amlodipine, hydrochlorothiazide, and losartan were observed in patients exhibiting poor adherence (n = 21) compared to adherent patients (n = 51) with statistical significance (p < 0.05). The method is promising for assessing antihypertensive adherence using dried plasma spots.

Enhanced external counterpulsation (EECP) augmentation of amlodipine in elderly patients with isolated systolic hypertension (ISH) and wide pulse pressure: A comparative study.

Ding Meili M, Zhang Jun J, Li Zuliang Z, Yang Jianqiao J

Geriatric patients with isolated systolic hypertension (ISH) and wide pulse pressure (PP) were treated using enhanced external counter pulsation (EECP) combined with amlodipine versus amlodipine alone. The efficacy of both treatment modalities was assessed based on hemodynamic parameters. Retrospectively included 132 elderly patients with ISH and wide PP in our hospital (Mar 2022-Jun 2024). After exclusion, 120 cases were analyzed and divided into the amlodipine group and the combined group. Primary indicators include endothelin-1 (ET-1), nitric oxide (NO), systolic blood pressure (SBP), PP, systemic vascular resistance (SVR), coronary flow reserve (CFR), flow-mediated vasodilatation (FMD); secondary measures include mean arterial pressure (MAP), wall shear stress (WSS) and adverse reaction incidence. After 4 courses of treatment, patients in the combined group had significantly lower rates of ET-1, SBP, PP, MAP, SVR and the incidence of adverse reactions (all P<0.05); NO, FMD, WSS and CFR were higher (all P<0.05) than in the amlodipine group. EECP plus amlodipine has advantages over amlodipine monotherapy in treating elderly patients with ISH and wide PP, which provides a scientific basis for optimizing clinical treatment.

Effect of dapagliflozin-spironolactone combination therapy versus monotherapy on albuminuria reduction and hyperkalemia risk in elderly patients with early type 2 diabetic nephropathy receiving high-dose RASi: A randomized controlled trial.

Chen Yingying Y, Liu Peng P, Chen Lili L, Zhang Fengmei F

This randomized controlled trial evaluated the efficacy and safety of dapagliflozin-spironolactone combination therapy versus monotherapy in reducing urinary albumin excretion rate (UAER) and mitigating hyperkalemia risk in elderly patients with early type 2 diabetic nephropathy (DN) receiving high-dose renin-angiotensin system inhibitors (RASi). In this prospective, open-label, parallel-group study, 168 elderly patients with early DN and mild-to-moderate hypertension were randomized to Group A (irbesartan 300 mg/d plus dapagliflozin 10 mg/d), Group B (irbesartan 300 mg/d plus spironolactone 20 mg/d), or Group C (irbesartan plus dapagliflozin and spironolactone). The primary endpoint was the change in UAER from baseline to week 72. Secondary outcomes included changes in blood pressure, serum potassium levels, and safety profiles. Baseline characteristics were well-balanced (P >0.05). Blood pressure remained comparable across groups during follow-up (P >0.05). After 72 weeks, intention-to-treat analysis showed that Group C achieved a significantly greater UAER reduction compared to Group A and Group B (P <0.05). Additionally, Group B exhibited higher serum potassium levels than Group A and Group C (P <0.05), leading to a higher discontinuation rate due to hyperkalemia (P <0.05). In elderly patients with early DN on high-dose RASi, dapagliflozin-spironolactone combination therapy achieved superior albuminuria reduction compared with either monotherapy, while attenuating the risk of spironolactone-associated hyperkalemia. Although no case of hyperkalemia occurred in the combination group in our trial, serum potassium was notably elevated relative to dapagliflozin monotherapy, underscoring the importance of regular monitoring in this population.

Bizarre Localization of Amlodipine-Induced AGEP Over Infiltrated Plaques of Borderline Lepromatous Leprosy in a Patient With Type-1 Lepra Reaction: An Uncanny Immunological Phenomenon.

Singhal Priyal P, Bhattacharya Ipshita I, Dsouza Paschal P, Chhaya et al.