cilnidipine / Generic mfg. - LARVOL DELTA

Greenness Assessment of HPLC-UV Method for Simultaneous Estimation of Four Antihypertensive Drugs. (PubMed, J Chromatogr Sci) - "An environmentally friendly HPLC method was developed to estimate angiotensin receptor blocker (telmisartan) and calcium channel blockers (cilnidipine, benidipine and azelnidipine) in a single run. To assess the environmental impact of the method, five greenness evaluation criteria, namely, the Green Analytical Procedure Index, Analytical GREEness, Chlortox Scale, Blue Applicability Grade Index, and Red-Blue-Green 12, were adopted. Concerning all the tools, the proposed method was found to be green."

Journal

Cilnidipine Cubosomal Nanogel Patch: Polymer-Nanostructure Synergy for Advanced Transdermal Drug Delivery. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The safety and biocompatibility were analyzed by skin irritancy studies and histology of rat skin, which revealed that the transdermal patches were non-irritant and safe for skin application. The study demonstrates an innovative drug delivery approach using cubosomes in transdermal patches for improved permeability, therapeutic efficacy, and sustained release."

Journal

Cost-Effective, Scalable Synthesis of Cilnidipine Nanocrystals for Enhanced Oral Bioavailability and Hypertension Treatment. (PubMed, Drug Dev Ind Pharm) - "CLN-NCs significantly improved in vitro solubility and dissolution, demonstrating a scalable preparation method suitable for industrial translation. This approach offers a promising pathway to enhance CLN's therapeutic efficacy in hypertension management."

HEOR • Journal • Cardiovascular • Hypertension

Anti-inflammatory potential of telmisartan compared to other antihypertensives: secondary outcomes from a randomized trial. (PubMed, Inflammopharmacology) - "The anti-inflammatory markers were reduced in both groups at 12 weeks without any statistically significant difference across groups. However, telmisartan was associated with greater reductions in hsCRP, IL-6, and TNF-α in patients with T2DM and hypertension following 12 weeks of treatment. These findings may indicate a potential anti-inflammatory effect of telmisartan that requires confirmation in adequately powered trials."

Journal • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Oncology • Type 2 Diabetes Mellitus • CRP • IL6 • PPARG • TNFA

LC-MS/MS-based simultaneous quantification of chlorthalidone and cilnidipine in rat plasma: Pharmacokinetic evaluation, green analytical assessment, and DoE-driven optimization. (PubMed, J Pharmacol Toxicol Methods) - "Detection was achieved in positive electrospray ionization mode using multiple reaction monitoring, with transitions of m/z 339.8909 → 85.0951 for chlorthalidone, m/z 493.5237 → 300.1587 for cilnidipine, and m/z 515.6423 → 342.6158 for telmisartan, employed as the internal standard. The method exhibited strong analyte stability and was successfully applied to the pharmacokinetic evaluation of both drugs in Wistar rats. This DoE-optimized LC-MS/MS platform offers a selective, reliable, and environmentally conscious analytical solution for the preclinical assessment of chlorthalidone and cilnidipine."

Journal • PK/PD data • Preclinical

Patterns of Prescription Switching in a Uniform-Pricing System for Multi-Source Drugs: A Retrospective Population-Based Cohort Study. (PubMed, Healthcare (Basel)) - "Switching rates varied substantially (coefficient of variation = 227%) by physician practice setting (e.g., public health center branches: 26%; tertiary hospitals: 15%) and by drug market size (e.g., glimepiride: 29%; cilnidipine: 1%). In Korea, physicians frequently switch prescriptions between originator and generic drugs, even as generic substitution at the pharmacy level remains uncommon. The substantial variation in MSPS across provider settings and drug markets-but not by patient characteristics-underscores the need for targeted pharmacy benefit policies to promote effective substitutability and competition among multi-source drugs."

Journal • Pricing • Retrospective data • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders

Green and White Analytical Chemistry: Advances, Comparisons, Future Perspectives, and a Proposal for Green Financing Model for Analytical Chemistry. (PubMed, J Pharm Sci) - "We analyze WAC's aspects within the development of stability-indicating High-Performance Thin-Layer Chromatography (HPTLC) methods for thiocolchicoside and aceclofenac. We further illustrate WAC's practical utility through the development of a green RP-HPLC method for azilsartan, medoxomil, chlorthalidone, and cilnidipine in human plasma, where a WAC-assisted AQbD strategy led to a validated, sustainable, and cost-effective procedure with an excellent white WAC score...This paper conducts a NOISE (needs, opportunities, improvements, strengths, exceptions) analysis of WAC, emphasizing the change it brings to existing Green Analytical Chemistry methodology. Finally, it proposes Green Financing for Analytical Chemistry (GFAC), a dedicated funding model designed to promote innovations which are aligned to GAC and WAC goals and bridge the gaps in current practices."

Financing • Journal • Review

Relative Evaluation of the benefit of Cilnidipine ON the Nature, Observational Indices, Temperature changes, and overall Effect in secondary Raynaud’s disease (RECONNOITER-1): Part B (ANZCTR) - P2 | N=38 | Recruiting | Sponsor: AISA Pharma Australia Pty. Ltd.

New P2 trial • Cardiovascular • Rheumatology

Reversion of a RND transporter pseudogene reveals latent stress resistance potential in Brucella ovis. (PubMed, PLoS Genet) - "Conversely, deleting bepE in Brucella abortus, a closely related zoonotic species that retains an intact version of the gene, increased its sensitivity to envelope disruptors in vitro and to cilnidipine in the intracellular niche. We conclude that bepE is a key determinant of chemical stress resistance in Brucella spp., and that its pseudogenization in B. ovis contributes to the documented hypersensitivity of this host-restricted lineage to chemical stressors."

Journal • Immunology

Reversion of a RND transporter pseudogene uncovers latent stress resistance in Brucella ovis. (PubMed, bioRxiv) - "To investigate the genetic basis of B. ovis susceptibility to dihydropyridine treatment, we selected for mutants capable of growing in the presence of cilnidipine...In other Brucella species, bepE remains intact, and we show that deleting this gene in the zoonotic pathogen Brucella abortus increases susceptibility to both dihydropyridine treatment and membrane-disrupting stress. Our study provides evidence that pseudogenes like bepE can serve as a latent reservoir of adaptive functions in B. ovis , including drug and stress resistance."

Journal • Cardiovascular • Hypertension • Immunology

Mechanistic investigation of methadone, tolfenamic acid, and cilnidipine in traumatic brain injury: a novel multi-target perspective outcome of network pharmacology. (PubMed, Inflammopharmacology) - "This study identified a primary target for MTD such as NOS1, NOS2, NOS3, DRD2, DAT (SLC6A3), MPO, SLC6A4, CXCR4-C-X-C, AKT1, SLC/8A2, HTR1A; for TA: MAPK1, GRIN1 and for CLD: IGF1R, DRD2, SHH, MAP2K1, CACNA1D, HTR2A, PDE4D, CASP3, MTOR, FASN, PTGS2, SCN9N, CNR1, CACNA1C, ABCB1, PIK3CA, GSK3B in the mechanistic regulation of TBI by reducing the activation of several pathways linked to development of TBI."

Journal • CNS Disorders • Vascular Neurology • ABCB1 • CASP3 • CXCR4 • DRD2 • FASN • HTR2A • MAP2K1 • MAPK1 • NOS1 • NOS2 • NOS3 • PACERR • PIK3CA • PTGS2 • SLC6A3 • SLC6A4

Thermodynamic Perspectives on the Impact of a Second Drug on Amorphous Drug Solubility. (PubMed, Mol Pharm) - "In this study, we experimentally determined how a second drug affects the amorphous solubility of ritonavir (RTV) and analyzed these effects from a thermodynamic perspective. Lopinavir (LPV), cilnidipine (CND), and probucol (PBC) were used as second drugs...In contrast, in the RTV/PBC system, the water content of the RTV-rich phase was more substantially decreased, leading to a higher experimentally determined value of RTV amorphous solubility than that predicted by ideal mixing of RTV and PBC. Overall, this study elucidates the impact of a second drug on the amorphous solubility of a primary drug and provides valuable insights for the design of supersaturated formulations containing multiple drugs."

Journal

Discovery of Cilnidipine Cocrystals with Enhanced Dissolution by the Use of Computational Tools and Semiautomatic High-Throughput Screening. (PubMed, Cryst Growth Des) - "Dissolution rates of drug and coformer were compared for better mechanistic understanding of the cocrystal dissolution-supersaturation-precipitation behavior. The case of cilnidipine with a rare occurrence of cocrystals emphasized the importance of using joint computational and HTS approaches to enable successful cocrystal identification for pharmaceutical development."

Journal

Cilnidipine: An L- and N-Type Blocker of Calcium Channels Ameliorating Renal Damage in Experimental Hypertensive Rats. (PubMed, Cureus) - "These results showed that in hypertensive experimental rats, cilnidipine, apart from its hypotensive actions, decreases proteinuria and urinary creatinine and Ang II levels. These actions of cilnidipine may be because of blocking N-type calcium channels. Therefore, cilnidipine dual L/N type CCB may act as a renoprotective drug and decrease glomerular damage. Further mechanistic studies using selective N-type channel blockers or knockout mice are needed to prove the findings."

Journal • Preclinical • Renal Disease

Formulation and evaluation of HPMC and pullulan-based rapidly dissolving films containing cilnidipine nanosuspension. (PubMed, Int J Biol Macromol) - "The CLD NS-RDF exhibited a significant increase in AUC0-24h, Cmax, and a decrease in Tmax and MRT as compared to the CLD CD-RDF. The CLD NS-RDF also had a superior effect to control the blood pressure in rats as compared to the CLD CD-RDF."

Journal • Cardiovascular • Hypertension

Synergistic action of cilnidipine and bexarotene in mitigating cholestatic liver damage: role of FXR signaling cascade. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Furthermore, the combined treatment upregulated the expression of FXR and its target genes, suggesting that the protective effects may be mediated through the activation of the FXR signaling cascade. These findings highlight the potential of cilnidipine and bexarotene as a novel therapeutic approach for the management of cholestatic liver disorders and provide insights into the underlying molecular mechanisms involving the FXR signaling pathway."

Journal • Cholestasis • Hepatology • Inflammation

Cilnidipine exerts antiviral effects in vitro and in vivo by inhibiting the internalization and fusion of influenza A virus. (PubMed, BMC Med) - "These findings highlight the promising anti-IAV properties of cilnidipine both in vitro and in vivo, suggesting its potential as a clinical agent for emergencies against influenza outbreaks."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Formulation and Evaluation of Polymeric Spherical Agglomerates-Based Porous Orodispersible Tablets of Cilnidipine. (PubMed, Pharmaceutics) - "The optimized formulation of porous ODTs (T3) displayed low friability (0.28 ± 0.03%), short disintegration time (6.26 ± 0.29 s), and quicker dissolution (94.16 ± 1.41% in 60 min) as compared to marketed tablet Cildipin® 10 mg (85 ± 2.3%). Thus, porous ODTs of CILSAs can rapidly release the drug, bypass gut metabolism, enhance oral bioavailability, and improve CIL's therapeutic effectiveness for angina and hypertension."

Journal • Cardiovascular • Hypertension

Hepatoprotective Effects of Cilnidipine in Cholestatic Liver Disease: Role of FXR and NRF2 Signalling. (PubMed, J Exp Pharmacol) - "Ursodeoxycholic acid (UDCA) treatment is ineffective for certain cholestatic diseases like benign recurrent intrahepatic cholestasis (BRIC), despite increasing the hydrophilic bile acid pool. Additionally, Cil decreased the oxidative stress level compared with that in the ANIT-treated group. The results suggest that Cil effectively treats cholestasis by affecting the FXR signaling system and the NRF2 pathway."

Journal • Cholestasis • Fibrosis • Gastroenterology • Hepatitis B • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Oncology • HMOX1 • NQO1 • SIRT1

Cilnidipine – a Novel CCB reduces blood pressure, heart rate and proteinuria in Indian Hypertensive Patients (ISN-WCN 2025) - "Conclusions Novel CCB Cilnidipine, added to existing drug regimens during routine clinical practice significantly reduces BP, heart rate and proteinuria in Indian hypertensive patients. The current study is one of the first real-world studies in India to assess the impact of cilnidipine on patients with essential hypertension using EMR data."

Clinical • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Renal Disease

AISA 021, a Novel Calcium Channel Antagonist in Development for Raynaud's & Systemic Sclerosis, Has Antagonistic Activity at Sodium Channel Targets for Pain Relief and Treats Scleroderma Pain Better Than Current Calcium Channel Blockers in a Phase 2A Study (ACR Convergence 2024) - "An N-type antagonist, ziconotide, is approved for neuropathic pain...Cilnidipine at the clinical concentration obtained from pk samples in the ongong Phase 2A study was found to more potently inhibit Nav1.7 in the closed state than gabapentin, amlodipine and bupivacaine, at similarly clinically relevant plasma concentrations...On the pain domain of the SHAQ, cilnidipine 10 mg(n=4) reduced pain by 27% but 62% with tadalfil 5 mg(n=5) , 20 mg(n=3) increased pain 12% but decreased pain 24% with tadalafil 5 mg(n=4), and placebo patients(n=4) reduced pain 4%... Cilnidipine seems to have clinically relevant inhibitory properties at Nav 1.7 and may have this at Nav 1.8 as well, based on structure activity relationship analysis and pending experimental determination. In a preliminary Phase 2 study, encouraging effects were seen in pain relief as reported by patients in addition to a reduction in the weekly frequency of Raynaud's attacks. Clinicians often combine a CCB with a..."

P2a data • Cardiovascular • Immunology • Neuralgia • Pain • Rheumatology • Scleroderma • Systemic Sclerosis • NAV1

Preliminary Results from the RECONNOITER Trial, a Phase 2 Study of AISA 021 in the Treatment of Secondary Raynaud's, Primarily Due to Systemic Sclerosis (ACR Convergence 2024) - "Dose groups were AISA-021 10mg and 20mg, alone and with tadalafil 5mg, tadalafil alone and placebo...Results replicate the improved 24 year safety record of cilnidipine in hypertension treatment in the SSc-RP population. In this preliminary safety and efficacy study, AISA-021 was well-tolerated and efficacy trends were seen. A published metanalysis of CCB use for RP finds AE frequency of >46% and treatment discontinuation in >30% of patients. (P= 0.02 for AISA-021 superiority on safety c/w CCBs)."

P2 data • Cardiovascular • Gastrointestinal Disorder • Hypertension • Immunology • Pain • Rheumatology • Scleroderma • Systemic Sclerosis

Modeling ventilation of patients with interstitial lung disease at rest and exercise: a bench study. (PubMed, BMC Pulm Med) - "In this bench study, we personalized a mechanical simulator thatmodels the lung inhomogeneity and spontaneous breathing of healthy subjects and ILD patients at rest and during exercise. Our results suggest that lung inhomogeneity could increase lung vulnerability to volo-atelec-trauma mechanisms in ILD. Further physiological studies are needed to evaluate the impact of this vulnerability on acute or chronic ILD worsening."

Journal • Interstitial Lung Disease • Mood Disorders • Pulmonary Disease • Respiratory Diseases

Enhanced Transdermal Delivery of Cilnidpine Via Ultradeformable Vesicle Loaded Patch: Statistical Optimization, Characterization and Pharmacokinetic Assessment. (PubMed, Pharm Nanotechnol) - "The study concludes that the transferosomal patches of CND offer a promising approach for effective transdermal delivery, potentially improving hypertension management for prolonged periods in a controlled manner."

Journal • PK/PD data • Cardiovascular • Hypertension

Lymphatic Targeting of Cilnidipine by Designing and Developing a Nanostructured Lipid Carrier Drug Delivery System. (PubMed, Drug Dev Ind Pharm) - "CLN NLCs significantly improved lymphatic delivery and proved to be effective in the treatment and management of hypertension. It has been proved that CLN NLCs are found to be better than any traditional CLN dosage form due to enhancement in solubility, absorption, bioavailability, intestinal permeability, avoidance of first-pass metabolism, P-glycoprotein efflux and reduction in dose-related side effects, achievement of controlled and sustained release action."

Journal • Cardiovascular • Hypertension