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olmesartan + azelnidipine (Rezaltas / Rezaltas)

✓ Approved

Daiichi Sankyo Company Limited · AGTR1 · Small Molecule

What is olmesartan + azelnidipine?

olmesartan + azelnidipine is a small molecule developed by Daiichi Sankyo Company Limited. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesRezaltas, Rezaltas
CompanyDaiichi Sankyo Company Limited
Drug ClassSmall Molecule
Molecular TargetAGTR1, CACNA1C
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Daiichi Sankyo Company Limited

Mechanism of Action

Molecular Targets

olmesartan + azelnidipine acts on 2 molecular targets:

AGTR1angiotensin II receptor type 1 (HAT1R, AT1)
CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

olmesartan + azelnidipine is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

Related Research Articles

PubMedJournal of the American Heart Association2026-10-07

Restricting Placental Transfer of Angiotensin Receptor Blockers to Mitigate Fetal Toxicity: A Potential Therapeutic Strategy for Preeclampsia.

Inaoka Naoko N, Iriyama Takayuki T, Ariyoshi Yu Y, Yoshida Yuri Y et al.

Enhanced AT1R (angiotensin II type 1 receptor) signaling contributes to preeclampsia development; however, angiotensin receptor blockers are contraindicated during pregnancy because of associated fetal toxicity. We aimed to determine whether chemical modification of an angiotensin receptor blocker restricts placental transfer while preserving maternal pharmacological activity. Polyethylene glycol-modified olmesartan derivatives were synthesized to increase molecular size and hydrophilicity and evaluated in vitro for AT1R inhibitory activity. Placental transfer was assessed using an angiotensin II-induced pregnant mouse model and an ex vivo human placental perfusion model to identify a derivative with reduced placental permeability. The selected compound was evaluated in vivo for pharmacological activity and fetal toxicity in pregnant mice. A series of polyethylene glycol-modified olmesartan derivatives maintained pharmacologically relevant AT1R inhibitory activity in vitro. Evaluation in angiotensin II-treated pregnant mice revealed compound #6, a polyethylene glycol-modified dimer containing an ionizable tertiary amine, which exhibited reduced placental transfer (∼7% relative to olmesartan). Consistently, compound #6 exhibited minimal transplacental transfer in the human placental perfusion model, comparable to insulin, a negative control. Regarding fetal toxicity, olmesartan induced neonatal renal developmental toxicity at doses as low as one tenth of its minimum effective dose, whereas compound #6 exhibited clear renal toxicity only above its effective dose, indicating a discernible safety margin. Restricting placental transfer through rational chemical modification enables decoupling of maternal efficacy from fetal toxicity of angiotensin receptor blockers. Although further optimization is required, these findings provide proof of concept that AT1R inhibition may represent a therapeutic strategy for preeclampsia during pregnancy.

PMID 42841504
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PubMedAmerican journal of preventive cardiology2026-10-05

Study design, rationale, and baseline characteristics of ATTAIN-HYPERTENSION, a phase 3 trial of the oral GLP-1 receptor agonist orforglipron for hypertension.

Laffin Luke L, Schlaich Markus P MP, Hall Michael E ME, Xie Cathy C CC et al.

Up to three-quarters of primary hypertension is epidemiologically attributed to excess adiposity. Incretin-based therapies are consistently associated with reduced blood pressure (BP) in clinical trials; however, no prior trial has investigated incretin-based therapies for hypertension treatment with BP as its primary efficacy outcome. ATTAIN-HYPERTENSION is a phase 3 master protocol directing two identical, randomized, placebo-controlled studies. Participants with BMI≥25kg/m2 and systolic BP (SBP)≥140 mmHg or diastolic BP (DBP)≥90 mmHg, independent of antihypertensive treatment, are randomized 2:1 to orforglipron or placebo. The study includes 5 periods: screening, a 4-week run-in during which treated participants change to standard background medications (olmesartan, amlodipine, hydrochlorothiazide), a 48-week treatment period including dose escalation and return to baseline antihypertensive medication, a 12-week randomized withdrawal period, and a 2-week safety follow-up. Primary end point is the change in office SBP at Week 36. Key secondary end points include change in ambulatory SBP, percent change in hsCRP, percent change in body weight, percent change in triglycerides and non-HDL cholesterol, and change in SBP across the randomized withdrawal period. ATTAIN-HYPERTENSION randomized 538 participants in Trial 1 and 546 in Trial 2 between April 2025 and January 2026 at 100 locations across 10 countries. The randomized population has a mean (SD) age of 53.7 (11.8) years, BMI of 35.6kg/m² (6.9), and office SBP of 144.2 mmHg (10.3). At screening, 55.4% of participants were treated with antihypertensive medication. ATTAIN-HYPERTENSION investigates the efficacy and safety of orforglipron for the treatment of hypertension in adults with overweight or obesity. Described here are the novel trial design, its rationale, and the enrolled population's baseline characteristics. (ClinicalTrials.gov: NCT06948422).

PMID 42830762
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PubMedPharmaceutics2026-09-26

A Thermoresponsive In Situ Salified Self-Nanoemulsifying Drug Delivery System of Olmesartan Medoxomil: Overcoming Leakage and Drug Trapping Limitations.

Sherif Abdelrahman Y AY, Altamimi Mohammad A MA, Elzayat Ehab M EM

Background/Objectives: Solid self-nanoemulsifying drug delivery systems (SNEDDS) prepared by adsorption onto porous carriers are widely used to improve the oral delivery of poorly water-soluble drugs. However, this approach is limited by increased dosing volume and incomplete drug release. This study aims to develop a thermoresponsive in situ salified SNEDDS (T-IS-SNEDDS) that simultaneously prevents formulation leakage and overcomes the release limitations of conventional adsorption-based solidification. Methods: Excipients were selected by solubility screening of oils and surfactants. Sodium and calcium carbonate were evaluated for in situ salt formation. Adsorption-based solid SNEDDS and thermoresponsive formulations containing poloxamer 188 with propylene glycol or polyethylene glycol 400 were prepared. Droplet size was measured after aqueous dilution. Solid-state characterization used scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. In vitro dissolution performance was evaluated against the raw drug and adsorption-based formulations. Results: Imwitor 308 and Tween 80 exhibited the highest solubilization capacities. Sodium carbonate (10 mg/g) markedly increased the solubility of olmesartan medoxomil from 4.11 ± 0.11 to 46.01 ± 1.92 mg/g. Although liquid in situ salified SNEDDS achieved rapid dissolution (94.2 ± 1.8% at 10 min), adsorption-based solidification required four capsules and yielded incomplete drug release (67.76 ± 3.18%). Both thermoresponsive formulations accommodated the therapeutic dose in a single capsule and released ≈95% of the drug within 60 min. Conclusions: The combined in situ salified drug loading and thermoresponsive matrix strategy successfully enables single capsule administration while overcoming the incomplete release of adsorption-based solid SNEDDS.

PMID 42797370
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PubMedPharmaceuticals (Basel, Switzerland)2026-09-26

Olmesartan-Loaded PLGA Nanoparticles Attenuate Methotrexate-Induced Kidney Injury: Association with the AT1R/ERK1/2 Signaling Axis.

Alawad Omar M OM, Tantawy Norhan N, Elsalhy Soha S, Ahmed Asmaa A AA et al.

Background/Objectives: Methotrexate (MTX) is an effective antineoplastic and immunosuppressive agent whose clinical use can be limited by nephrotoxicity. Increasing evidence suggests that dysregulated angiotensin II-mediated signaling contributes to MTX-induced renal injury. Olmesartan (OLM), an angiotensin II type 1 receptor (AT1R) blocker, possesses renoprotective properties; however, its therapeutic efficacy may be limited by suboptimal pharmacokinetics and tissue deli\very. This study aimed to develop OLM-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (OLM-PLGA) and investigate their nephroprotective efficacy and underlying molecular mechanisms in MTX-induced nephrotoxicity. Methods: OLM-PLGA nanoparticles were prepared and evaluated for their physicochemical characteristics. The in vivo nephroprotective effects of OLM-PLGA were investigated in male Sprague-Dawley rats, which were allocated into four groups: OLM (10 mg/kg), OLM-PLGA (10 mg/kg), MTX-treated, and normal control. Renal function, oxidative stress, inflammation, apoptosis, and fibrosis were assessed, together with renal gene expression of AT1R and extracellular signal-regulated kinase 1/2 (ERK1/2). Results: Compared with free OLM, OLM-PLGA provided superior protection against MTX-induced renal dysfunction and oxidative stress, as evidenced by improved renal function and enhanced antioxidant defense. OLM-PLGA also exerted greater anti-inflammatory and anti-apoptotic effects and attenuated renal fibrotic changes, accompanied by reduced renal expression of α-smooth muscle actin and collagen. These protective effects were associated with decreased AT1R gene expression and suppression of downstream ERK1/2 signaling. Conclusions: PLGA-based nanoencapsulation enhanced the nephroprotective efficacy of OLM against MTX-induced nephrotoxicity and was associated with the modulation of the AT1R/ERK1/2 signaling axis. OLM-PLGA may therefore represent a promising nanotherapeutic approach for improving OLM delivery and renal protection during MTX treatment.

PMID 42797507
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PubMedJournal of hazardous materials2026-09-25

Back-transformation and dual-type metabolites associated with pharmaceutical negative removal and residual ecological risks in biological treatment.

Jang Heewon H, Kang Daeho D, Jeon Junho J

Pharmaceuticals entering wastewater treatment plants undergo complex biological transformations to generate transformation products (TPs). However, the formation mechanisms and environmental impacts of these TPs remain insufficiently understood. In this study, an integrated LC-HRMS monitoring workflow combining target, suspect, and non-target screening (SNTS) was applied to characterize pharmaceutical biotransformation within a biological reactor (BR). A total of 37 pharmaceuticals and 39 TPs were detected, including 6 TPs quantified by target screening and 33 tentatively identified through SNTS. Major reactions included dealkylation and hydroxylation, and several previously unreported TPs were detected, including losartan-derived products (M435, M437) and fenbufen-derived products (FBF-M225). Fold-change analysis enabled classification of TPs into human-derived, microbial-derived, and dual-type metabolites. Notably, human- and dual-type metabolites were closely associated with negative removal phenomena and secondary TP formation, suggesting overlapping processes of back-transformation and in situ microbial conversion within the BR. Structure-based PMT/PBT assessments and risk quotient analysis indicated that several TPs, including CFN-M209, LST-M421, and LST-M435, exhibited higher persistence, mobility, bioaccumulation potential, or ecological risk than their parent compounds. In addition, parent compounds such as olmesartan and climbazole exhibited RQ values greater than 1, indicating potential ecological risks to aquatic organisms. Mixture risk assessment further highlighted cumulative ecological concerns in wastewater effluent, particularly for CBZ and its associated TPs. These findings indicate that the modified sequencing batch reactor (MSBR) examined in this study inherently generates environmentally relevant TPs, and that environmental risk assessment should extend beyond parent compounds to include both human-derived metabolites and treatment-induced TPs, thereby supporting more comprehensive and sustainable wastewater management strategies.

PMID 42790035
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PubMedJournal of geriatric cardiology : JGC2026-09-19

Blood pressure lowering efficacy of sacubitril/allisartan versus olmesartan in elderly Chinese hypertensive patients.

Zhang Wei W, Yan Jie J, Zhang Jin J, Ge Qian Q et al.

Sacubitril/Allisartan, a novel angiotensin receptor-neprilysin inhibitor, has demonstrated antihypertensive efficacy in patients with hypertension. Its effects in the elderly patients, who often present with increased arterial stiffness and comorbidities, remain less understood. We performed analysis of data from a randomized clinical trial that compared the blood pressure-lowering effect at 12 weeks of treatment with sacubitril/allisartan (240 mg/d or 480 mg/d) and olmesartan (20 mg/d). Eligible patients with mild-to-moderate hypertension and aged 65-75 years were included in the analysis. The primary outcome was change in clinic and 24-hour ambulatory blood pressure from baseline to week 12. Of the 1197 randomized patients, 338 elderly patients (41.5%) (mean age: 67.9 ± 2.3 years, 49.9% male) were included in this analysis. Baseline characteristics were comparable among treatment groups. At 12 weeks, least square mean (± standard error) changes from baseline in clinic systolic/diastolic blood pressure in the sacubitril/allisartan (240 mg/d or 480 mg/d) group and the olmesartan (20 mg/d) group were -24.0 ± 1.6/-5.7 ± 0.9 mmHg, -26.2 ± 1.6/-6.5 ± 0.9 mmHg, and -21.5 ± 1.6/-6.3 ± 0.9 mmHg, respectively. Greater reductions were also observed with sacubitril/allisartan (480 mg) compared with olmesartan (20 mg) in 24-hour, daytime and nighttime systolic blood pressure (all P-values < 0.05). The reductions in ambulatory blood pressure were dose-dependent (P = 0.007), and significantly greater with sacubitril/allisartan (480 mg) compared with olmesartan (20 mg) for nighttime blood pressure [-17.5 ± 1.8/-8.1 ± 1.0 mmHg, with a difference of -10.9 mmHg (-16.1 to -5.8, P < 0.0001) for systolic blood pressure and -4.5 mmHg (-7.3 to -1.8, P = 0.002) for diastolic blood pressure]. In elderly patients with hypertension, sacubitril/allisartan provided dose-dependent greater blood pressure reductions compared with olmesartan.

PMID 42760954
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