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amlodipine + celecoxib (Consensi / KIT 302 / KIT302)

✓ Approved

Burke Pharmaceutical · CACNA1C · 小分子

什么是 amlodipine + celecoxib？

amlodipine + celecoxib 是一种小分子，由Burke Pharmaceutical研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Consensi, KIT 302, KIT302
公司Burke Pharmaceutical
药物类别小分子
分子靶点CACNA1C, PTGS2
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Burke Pharmaceutical

作用机制

分子靶点

amlodipine + celecoxib 作用于 2 个分子靶点：

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (NEDHLSS, CACH2)
PTGS2prostaglandin-endoperoxide synthase 2 (hCox-2, PHS-2)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

amlodipine + celecoxib 针对 3 个适应症，涉及 3 个治疗领域。

治疗领域疾病/病症分期
Vascular disordersHypertension✓ Approved
Musculoskeletal and connective tissue disordersMusculoskeletal pain✓ Approved
Renal and urinary disordersRenal failurePreclinical

相关研究文献

PubMedHigh blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension2026-10-26

A Practical Treatment Platform Version 3.0 for Using Angiotensin Receptor Blocker-Based Single-Pill Combinations in Patients With Hypertension.

Tocci Giuliano G, Burnier Michel M, de la Sierra Alejandro A, Grassi Guido G et al.

Elevated blood pressure (BP) is the leading cause of cardiovascular disease and a major contributor to mortality, affecting almost one third of the adult population worldwide. Despite strong scientific evidence, guidelines and multiple therapeutic options, many patients remain undertreated or uncontrolled, largely due to poor medication adherence and medical inertia. Complexity of multi-pill regimens contributes significantly to non-adherence, whereas single-pill combinations (SPCs) improve adherence and persistence, accelerate BP control, and promote better long-term outcomes than multiple combinations. Appropriate selection of SPC in individual hypertensive patients may be a difficult though very important task for physicians. Thus, development of tools that may facilitate use of SPC in clinical practice is desirable. Among renin-angiotensin system blockers, olmesartan (OM) has demonstrated sustained efficacy, favourable tolerability, both as monotherapy and in SPCs with amlodipine and/or hydrochlorothiazide, which are available in multiple dosages. The present OM-based platform builds on earlier frameworks and incorporates guidelines' updates complemented by a systematic review of available literature. This "3.0" proposal expands patient categorization to include comorbidities or complications often overlooked in clinical practice guidelines, providing a practical, evidence-based approach to support individualized hypertension management complementing guideline recommendations.

PMID 42928416
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PubMedEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V2026-10-25

Bovine serum Albumin-Mediated effects on colonic Solubility, mucus Permeation, and absorption of celecoxib.

D Suljovic S, J Plum P, R Berthelsen B, O Scherf-Clavel SC et al.

Celecoxib was used as a model compound in fasted state simulated colonic fluid (FaSSCoF) to investigate equilibrium drug solubility (Seq), protein binding using rapid equilibrium dialysis (RED), flux and permeability (Papp) across porcine colonic mucus (PCM), and in vivo colonic absorption using a rat intracolonic instillation model. The primary focus was on the role of bovine serum albumin (BSA) as a solubilizing and binding constituent, while bile salts (sodium taurodeoxycholate, TDC) with lecithin and poloxamer 407 were included as comparative systems to evaluate how differences in solubilizer type influence celecoxib permeability and absorption. BSA demonstrated a pronounced solubilizing effect on celecoxib with a 1:1 M binding ratio, increasing the apparent Seq from 5.1 µg/mL to 92 µg/mL in FaSSCoF containing 15 mg/mL BSA. Under these conditions, diffusion across PCM increased approximately seven-fold compared with FaSSCoF without BSA, accompanied by a four-fold increase in colonic absorption in vivo. In contrast, when celecoxib concentration was maintained constant and BSA was subsequently added to FaSSCoF, diffusion across PCM decreased up to ten-fold at BSA concentrations of 1.5 mg/mL, accompanied by an approximately 30 % decrease in colonic absorption in vivo. This behavior is consistent with an increased BSA-bound fraction and a reduced free drug concentration available for transport. The addition of TDC with lecithin or poloxamer 407 similarly increased celecoxib diffusion across PCM and colonic absorption when celecoxib was dissolved at Seq in FaSSCoF, although no statistically significant differences were observed between the solubilizing systems. Overall, these findings demonstrate that solubilizing constituents in colonic fluids can substantially increase drug solubility, mucus permeation, and colonic absorption, highlighting the importance of accounting for protein-drug interactions when evaluating drug behavior in the colon.

PMID 42926029
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PubMedPakistan journal of pharmaceutical sciences2026-10-25

Amlodipine besylate and valsartan combined mucoadhesive buccal patch formulations: In-vitro release and ex-vivo permeation studies.

Anwar Nosheen N, Gul Rahman R, Jan Syed Umer SU, Shahwani Ghulam Razaque GR et al.

Oral fixed-dose combinations of Amlodipine Besylate and Valsartan are widely prescribed for hypertension but are associated with first-pass metabolism and variable bioavailability. Buccal drug delivery provides a favorable substitute to improve systemic availability and provide sustained release. This study aimed to develop and assess mucoadhesive buccal patches containing Amlodipine Besylate and Valsartan to enhance bioavailability and achieve controlled drug release over 24 hours. Buccal patches were developed via the solvent-casting method using Hydroxypropyl Methylcellulose, Polyvinylpyrrolidone, Methylcellulose, Sodium Alginate and Metolose as backing membrane polymers. All the prepared films were evaluated for physicochemical parameters by means of X-ray Diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and in vitro and ex vivo drug release. In-vitro drug release was studied with USP Apparatus II (paddle method) in 500 ml 6.8 pH phosphate buffer at 37 ± 0.5°C and 50 rpm for 24 hours. Ex vivo permeation studies were performed using a Franz diffusion cell fitted with rabbit buccal mucosa under similar conditions. The formulations generally exhibited acceptable physicochemical characteristics within the evaluated parameters. The developed films appeared transparent with a uniform distribution of components. FTIR analysis did not indicate any detectable incompatibility or significant interaction between the drugs and excipients under the study conditions. Among all formulations, F1 contained the highest drug release and permeation. After 24 hours, cumulative release reached 84.45% for amlodipine and 88.03% for valsartan. Ex-vivo permeation was 76.31% and 78.42% for amlodipine and valsartan, respectively. Furthermore, buccal films' histopathological and stability studies were found to be harmless and functioned as an efficient dosage system. The developed mucoadhesive buccal patches successfully delivered both drugs in a sustained manner. Formulation F1 showed superior release and permeation profiles, suggesting its potential as substitute to conventional oral dosage forms for improved hypertension management.

PMID 42924971
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PubMedRSC advances2026-10-25

Innovative design and development of novel thiazole-paracetamol hybrids as COX inhibitors and immunomodulatory activity: design, synthesis, SAR, in vitro biological evaluation, and molecular docking analysis.

Salem Mohamed A MA, Ayman Radwa R, Ammar Yousry A YA, Abusaif Moustafa S MS et al.

The hybridization approach was employed to design a single pharmacophore based on the conjugation of paracetamol with thiazole derivatives, yielding thiazole-paracetamol hybrid derivatives 4-11 that utilize a linker from hydrazone (-C[double bond, length as m-dash]N-NH) and azo (-N[double bond, length as m-dash]N-) linkers, serving as the hydrogen bond donor/acceptor binding site. The structure of the designed derivatives was fully characterized and confirmed using analytical data (IR, 1H NMR, and 13C NMR), and elemental analysis. The anti-inflammatory potential of the synthesized hybrids was evaluated using in vitro COX-2 enzymatic inhibition assay. The compounds exhibited moderate to excellent COX-2 inhibitory activity, with IC50 values ranging from 0.81 to 7.27 µM, compared with celecoxib (IC50 = 0.62 ± 0.02 µM). Among the synthesized derivatives, the 5-acetyl-4-methylthiazole candidate 8 emerged as the most potent inhibitor, displaying an IC50 value of 0.81 ± 0.02 µM, whereas the 5-ethoxycarbonyl-4-methylthiazole derivative 7 also demonstrated pronounced activity (IC50 = 1.35 ± 0.15 µM). The SAR analysis revealed that the 4-methylthiazole scaffold was more favorable for COX-2 inhibition than the corresponding 4-oxo-4,5-dihydrothiazole scaffold, while the introduction of compact carbonyl-containing substituents at the C-5 position markedly enhanced inhibitory potency. In contrast, aromatic substitution or incorporation of a 4-oxo-4,5-dihydrothiazole ring reduced activity. Furthermore, compounds 7 and 8 exhibited low-micromolar COX-1 inhibitory activity (IC50 = 0.89 ± 0.05 and 0.72 ± 0.02 µM, respectively), demonstrating dual activity toward COX-1/2 inhibition. In addition, compound 8 effectively suppressed the production of TNF-α and IL-6, with IC50 values of 1.48 ± 0.50 and 1.80 ± 0.35 µM, respectively, showing inhibitory activity comparable to that of celecoxib (IC50 = 1.40 ± 0.10 and 1.74 ± 0.20 µM, respectively). The docking process of the most promising derivative 8 demonstrated strong binding affinity and various types of interactions, including hydrogen bonding, π-π stacking, and hydrophobic interactions (π-alkyl and alkyl). In addition, ADMET prediction indicated a favorable pharmacokinetic profile and acceptable toxicity levels. These findings identify compound 8 as a promising lead candidate for the development of next-generation anti-inflammatory agents with dual cyclooxygenase inhibitory and immunomodulatory properties.

PMID 42921339
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PubMedPharmacotherapy2026-10-25

A Model for Estimating the Risk of Gastrointestinal Bleeding for Patients on Oral Anticoagulants and Interacting Medications.

Gomez-Lumbreras Ainhoa A, Tawfik Abdelrahman G AG, Reese Thomas T, Witt Daniel M DM et al.

Pharmacodynamic drug-drug interactions (DDI) in patients receiving oral anticoagulants (OAC) may increase the risk of gastrointestinal bleeding (GIB). The purpose of this study was to develop and validate a GIB model for patients receiving OACs. A risk model, Drug Interactions in Oral AntiCoagulants for Risk of Gastrointestinal Bleeding (DIOAC-GIB), was developed to predict GIB based on interacting medications and other patient-specific risk factors for patients on OAC. Inputs for the model were obtained using random-effect meta-analysis or from the literature for the following attributes: exposure to nonsteroidal anti-inflammatory drugs (NSAIDs); selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs); aspirin, antiplatelet medications, and proton pump inhibitors (PPIs); age; and GIB history. The model was correlated to existing OAC models (HAS-BLED and DOAC score). GIB risk for OACs was based on pivotal trials (1.16% for apixaban; 3.15% for rivaroxaban; 3.00% for dabigatran; 3.31% for edoxaban; and 2.00% for warfarin). The odds ratio (OR) of GIB for NSAIDs ranged from 1.16 (95% confidence interval [CI]: 0.84-1.61) for celecoxib to 20.67 (95% CI: 14.56-29.34) for ketorolac. ORs for GIB among SSRI/SNRIs ranged from 1.31 (95% CI: 1.07-1.62) for paroxetine to 1.50 (95% CI: 1.32-1.70) for venlafaxine. Risk of GIB also included persons > 65 years of age (relative risk = 2.50, 95% CI: 1.2-5.5); history of GIB (OR = 5.14, 95% CI: 3.92-6.73); exposure to aspirin (OR = 1.31, 95% CI: 0.93-1.85), antiplatelet medications (OR = 1.97, 95% CI: 1.73-2.25), and corticosteroids (OR = 1.69, 95% CI: 1.53-1.87); and PPIs reduced GIB risk (OR = 0.67, 95% CI: 0.62-0.74). Correlations between the DIOAC-GIB and HAS-BLED and DOAC scores were 0.5 for both (p < 0.01). DIOAC-GIB is a novel GIB-risk model that incorporates pharmacodynamic OAC DDIs to assist clinicians and patients to determine a therapeutic plan while accounting for GIB risk. DIOAC-GIB correlates with other bleeding risk scores and may help identify high-risk patients who may benefit from tailored prescribing.

PMID 42927649
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PubMedJournal of medicinal chemistry2026-10-23

Strategic Development of Activatable Turn-On Fluorogenic Prodrugs of Celecoxib with Selective Anticancer Activity and Attenuated Cardiotoxicity.

Misra Roopjyoti R, Barman Pallavi P, Das Dorothy D, Bala Asis A et al.

Herein, we report the first examples of ROS-responsive fluorogenic prodrugs that enable sustained intracellular delivery of celecoxib with a fluorescence turn-on readout and exhibit selective anticancer activity with reduced cardiotoxicity. Spectroscopic and HPLC analysis confirmed efficient ROS-mediated activation and time-dependent release of both celecoxib and the fluorophore, providing mechanistic insights into the stimuli-triggered prodrug activation and the self-immolative drug release profile under physiological conditions. The lead prodrug Cou-Coxib exhibited selective anticancer activity in triple-negative breast cancer (MDA-MB-231) cells over non-malignant cells and showed excellent therapeutic efficacy by S phase arrest. Furthermore, Cou-Coxib ameliorated celecoxib-induced cardiotoxicity in H9C2 cardiomyoblasts. The fluorogenic drug delivery process was validated with turn-on fluorescence readout in aqueous and cellular media and subsequently in developing zebrafish embryos. Overall, this study underscores the rational design of fluorogenic prodrugs of celecoxib exhibiting selective anticancer activity in breast cancer with attenuated cardiotoxicity, thereby offering improved therapeutic potential.

PMID 42916692
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