Manidipine hydrochloride 10mg tablets

Chyloperitoneum (chylous ascites) is a rare complication of peritoneal dialysis (PD). Its causes may be traumatic and nontraumatic, associated with neoplastic disease, autoimmune disease, retroperitoneal fibrosis, or rarely calcium antagonist use. We describe six cases of chyloperitoneum occurring in patients on PD as a sequel to calcium channel blocker use. The dialysis modality was automated PD (two patients) and continuous ambulatory PD (the rest of the patients). The duration of PD ranged from a few days to 8 years. All patients had a cloudy peritoneal dialysate, characterized by a negative leukocyte count and sterile culture tests for common germs and fungi. Except for in one case, the cloudy peritoneal dialysate appeared shortly after the initiation of calcium channel blockers (manidipine, n = 2; lercanidipine, n = 4), and cleared up within 24–72 h after withdrawal of the drug. In one case in which treatment with manidipine was resumed, peritoneal dialysate clouding reappeared. Though turbidity of PD effluent is due in most cases to infectious peritonitis, there are other differential causes including chyloperitoneum. Although uncommon, chyloperitoneum in these patients may be secondary to the use of calcium channel blockers. Being aware of this association can lead to prompt resolution by suspension of the potentially offending drug, avoiding stressful situations for the patient such as hospitalization and invasive diagnostic procedures.

Abstract licence: CC BY

Elevated de novo lipid synthesis is a remarkable adaptation of cancer cells that can be exploited for therapy. However, the role of altered lipid metabolism in the regulation of apoptosis is still poorly understood. Using thermal proteome profiling, we identified Manidipine-2HCl, targeting UGT8, a key enzyme in the synthesis of sulfatides. In agreement, lipidomic analysis indicated that sulfatides are strongly reduced in colorectal cancer cells upon treatment with Manidipine-2HCl. Intriguingly, this reduction led to severe mitochondrial swelling and a strong synergism with BH3 mimetics targeting BCL-XL, leading to the activation of mitochondria-dependent apoptosis. Mechanistically, Manidipine-2HCl enhanced mitochondrial BAX localization in a sulfatide-dependent fashion, facilitating its activation by BH3 mimetics. In conclusion, our data indicates that UGT8 mediated synthesis of sulfatides controls mitochondrial homeostasis and BAX localization, dictating apoptosis sensitivity of colorectal cancer cells.

Abstract licence: CC BY

Cell wall deficient "L- form" bacteria are of growing medical interest as a possible source of recurrent or persistent infection, largely because of their complete resistance to cell wall active antibiotics such as β-lactams. Antibiotics that specifically kill L-forms would be of potential interest as therapeutics, but also as reagents with which to explore the role of L-forms in models of recurrent infection. To look for specific anti-L-form antibiotics, we screened a library of several hundred FDA-approved drugs and identified compounds highly selective for L-form killing. Among the compounds identified were representatives of two different classes of calcium channel blockers: dihydropyridines, e.g., manidipine; and diphenylmethylpiperazine, e.g., flunarizine. Mode of action studies suggested that both classes of compound work by decreasing membrane fluidity. This leads to a previously recognized phenotype of L-forms in which the cells can continue to enlarge but fail to divide. We identified a considerable degree of variation in the activity of different representatives of the two classes of compounds, suggesting that it may be possible to modify them for use as drugs for L-form-dependent infections.

Abstract licence: CC BY

Background: Multidrug resistance (MDR), primarily driven by P-glycoprotein (P-gp)-mediated drug efflux, presents a significant challenge in cancer therapy, contributing to chemotherapy failure and poor patient outcomes. Objectives: In this study, we explored the potential of manidipine (MA), a clinically approved calcium channel blocker, to reverse P-gp-mediated MDR through modulation of calcium signaling via nuclear factor of activated T cells 2 (NFAT2). Methods: Paclitaxel (PTX) resistance ABCB1-overexpressing cancer in vitro and in vivo were used for evualting the anti-MDR effects of MA, as well as the underlying mechanism with siRNA of NFAT2. Results: We found that MA at non-toxic concentrations (0.6–5.4 μM) significantly sensitize drug-resistant colorectal (HCT-8/T) and non-small cell lung (A549/T) cells to PTX, reducing its IC50 by up to 1328-fold in vitro models. Mechanistically, MA inhibited P-gp efflux activity without altering its expression, as shown by an increased intracellular accumulation of doxorubicin and Flutax-2 (2.3- and 3.1-fold, respectively) and dose-dependent modulation of ATPase activity (EC50 = 4.16 μM). Notably, MA reduced intracellular calcium levels (52% reduction, p < 0.001) and downregulated NFAT2, an oncogene overexpressed in resistant cells. In vivo, MA (3.5 mg/kg) synergizes with PTX to inhibit tumor growth by 68% (p < 0.001) in A549/T xenograft model, without an observable decrease in weight. Conclusions: In sum, all these results position MA as a novel NFAT2 inhibitor to overcome P-gp-mediated MDR via modulating calcium signaling, which points to further investigation for its clinical applications.

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The aim of current research is to develop a liquid supersaturable self-nanoemulsifying drug delivery system (S-SNEDDS) of manidipine for enhancing the solubility and dissolution rate. Cithrol GMS – Cerex ELS250 – Propylene Glycol laurate are chosen based on the maximum solubility of manidipine and were used to construct ternary phase diagrams with Smix in 3:1 ratio and 20 mg drug loading was done and evaluated for entrapment efficiency, drug content and in-vitro drug release. To choose a precipitation inhibitor, in-vitro precipitation studies were carried out, and supersaturable SNEDDS were made the prepared formulations were evaluated and final optimised one is characterised for FTIR, SEM, globule size, zetapotential and stability studies. Out of all formulation F14 exhibited good results with highest drug content of 98.45±1.39% and entrapment efficiency of 98.91±1.70 % and drug release of 98.21% in 60min. F14 with PVP K17 (2%) precipitation inhibitor (SF14) exhibited drug content of 99.05% and entrapment efficiency was 99.75% which was almost >1% higher when compared to manidipine SNEDDS (F14). Manidipine S-SNEDDS (SF14) had the maximum drug release (99.85%) in 60min. SF14 S-SNEDDS had a mean globule size of 162.3 nm and zeta potential (mean) values ranged between -13.1 mV. The FT-IR, SEM and stability studies confirmed the complexation of manidipine and amorphous state of the drug and formulation to be stable for 3 months. Thus, this study indicated that the solid SNEDDS could be used as a potential drug carrier for manidipine with improved solubility and dissolution rate.

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This study presents a comprehensive evaluation and environmental risk assessment (ERA) of pharmaceutical residues in the Cerrón Grande Reservoir, one of the most important surface water bodies in El Salvador. Sampling campaigns were conducted over a one-year period, covering both the dry (January 2024) and rainy (July 2024) seasons. A total of 76 pharmaceutical compounds were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), of which only five were not detected. During the dry season, the highest environmental concentrations were observed for mecamylamine (1710–6913 µg L−1), 1,7-dimethylxanthine (379–2829 µg L−1), chloroquine (2.29–362.7 µg L−1), and hydroxychloroquine (5.02–315.4 µg L−1). Concentrations generally decreased in the rainy season, with mecamylamine (1526–2198 µg L−1), 1,7-dimethylxanthine (0.018–0.55 µg L−1), and caffeine (0.2–0.474 µg L−1) remaining the most prevalent. Compounds exceeding 1 µg L−1 were assessed using predicted no-effect concentrations (PNEC) to calculate risk quotients (RQ). Chloroquine (RQ = 3346.3), mecamylamine (RQ = 1437.8), hydroxychloroquine (RQ = 1027.2), and manidipine (RQ = 271.0) posed the highest risks during the dry season, while only mecamylamine (RQ = 502.0) exceeded this threshold in the rainy season. To our knowledge, this represents the first in-depth study of pharmaceutical residues in Salvadoran surface waters, providing a foundational reference for future research and environmental policy in the region.

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Manidipine (MP) is widely used for reducing high blood pressure. Calslot® (CALS) tablets, which are the original MP medicines, and their generic medicines have been used for patients in clinical situations. The authors hypothesized that the photodegradability of MP drug substance in CALS tablets might be enhanced when the tablets were photo-exposed after the change of the dosage form by the presence of riboflavin (RF), which is utilized as a coloring agent and a well-known photosensitizer. The present study clarified that RF enhanced the photodegradation of MP when the powders and the suspensions of CALS tablets were ultraviolet light (UV) irradiated. The addition of RF to the suspension of MP standard substances also promoted MP photodegradation along with the increase of the generation rate of its main photoproduct, benzophenone. Finally, the authors performed the photostabilization of MP suspensions based on the addition of quercetin (QU), which is one of polyphenols and has both the antioxidative potency and the UV filtering potency. It is summarized that QU has a protective potency for MP’s own photodegradation, and it partially suppresses the photocatalytic effect of RF. Further studies focused on the photochemical behaviors of utilized additives for medicines are needed for their safe use.

Abstract licence: CC BY