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Forensic Science International Nov 2020Amlodipine is a dihydropyridine calcium channel blocker widely used in the treatment of high blood pressure and coronary heart disease. Intoxication can lead to reflex...
Amlodipine is a dihydropyridine calcium channel blocker widely used in the treatment of high blood pressure and coronary heart disease. Intoxication can lead to reflex tachycardia following massive hypotension and death. The objective of this work was to study the post-mortem concentrations of amlodipine in 62 patients in order to determine whether the use of the reference concentrations from the living patients was applicable in postmortem setting, and to define more precisely the fatal and non-fatal postmortem concentrations of amlodipine. The amlodipine concentrations were measured in femoral whole blood by LC-MS/MS validated method. When sufficient information was available, the data were classified into 2 different groups, based on the conclusions of the autopsy and toxicological results: G1: non-toxic death and G2: fatal poisoning involving amlodipine alone or as part of a multidrug poisoning. The median concentration of amlodipine [1st quartile - 3rd quartile] of the whole population (n = 62) was 81 [42-134] ng/mL. Twenty-two cases were classified as G1 and thirteen as G2. The observed median [1st quartile - 3rd quartile] concentration of amlodipine was 66 [40.5-79.5] ng/mL in G1 and 240 [170-404] ng/mL in G2. The median concentrations observed in "non-toxic" deaths (66 ng/mL) were three times higher than those usually observed in living patients. Amlodipine distribution ratio between plasma and whole blood concentrations seems insufficient to explain this difference and postmortem redistribution from organs should be considered, and could suggest the same redistribution pattern for other drugs belonging to the same family.
Topics: Aged; Amlodipine; Calcium Channel Blockers; Chromatography, Liquid; Female; Forensic Toxicology; Humans; Male; Mass Spectrometry; Postmortem Changes
PubMed: 33152659
DOI: 10.1016/j.forsciint.2020.110555 -
Pharmacology Research & Perspectives Apr 2023This study was designed to evaluate the synergism of two couples of antihypertensive drugs (amlodipine + telmisartan and amlodipine + candesartan) on blood...
This study was designed to evaluate the synergism of two couples of antihypertensive drugs (amlodipine + telmisartan and amlodipine + candesartan) on blood pressure reduction in vivo by both SynergyFinder 3.0 and probability sum test. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (0.5, 1, 2, and 4 mg/kg), telmisartan (4, 8, and 16 mg/kg), candesartan (1, 2, and 4 mg/kg), nine combinations for amlodipine and telmisartan, and nine combinations for amlodipine and candesartan. The control rats were treated by 0.5% carboxymethylcellulose sodium. Blood pressure was recorded continuously up to 6 h after administration. Both SynergyFinder 3.0 and the probability sum test were used to evaluate the synergistic action. The synergisms calculated by SynergyFinder 3.0 are consistent with the probability sum test both in two different combinations. There is an obviously synergistic interaction between amlodipine and telmisartan or candesartan. The combinations of amlodipine and telmisartan (2 + 4 and 1 + 4 mg/kg) and amlodipine and candesartan (0.5 + 4 and 2 + 1 mg/kg) might exert an optimum synergism against hypertension. Compared with the probability sum test, SynergyFinder 3.0 is more stable and reliable to analyze the synergism.
Topics: Rats; Animals; Telmisartan; Blood Pressure; Amlodipine; Antihypertensive Agents; Hypotension; Rats, Inbred SHR
PubMed: 36810974
DOI: 10.1002/prp2.1064 -
Antimicrobial Agents and Chemotherapy Jul 2020Mining existing agents that enhance the therapeutic potential of ergosterol biosynthesis inhibitors (EBI) is a promising approach to improve Chagas disease chemotherapy....
Mining existing agents that enhance the therapeutic potential of ergosterol biosynthesis inhibitors (EBI) is a promising approach to improve Chagas disease chemotherapy. In this study, we evaluated the effect of ravuconazole, an EBI, combined with amlodipine, a calcium channel blocker, upon experimental infection. assays confirmed the trypanocidal activity of both compounds in monotherapy and demonstrated an additive effect (sum of the fractional inhibitory concentration [ΣFIC] > 0.5) of the combined treatment without additional toxicity to host cells. experiments, using a murine model of the Y strain in a short-term protocol, demonstrated that amlodipine, although lacking trypanocidal activity, dramatically increased the antiparasitic activity of underdosing ravuconazole regimens. Additional analysis using long-term treatment (20 days) showed that parasitemia relapse until 60 days after treatment was significatively lower in mice treated with the combination (4 out of 14 mice) than ravuconazole monotherapy (10 out of 14 mice), even in the presence of immunosuppressant pressure. Furthermore, the combined therapy was well tolerated and protected the mice from mortality. The treatments also impacted on the cellular and humoral immune response of infected animals, inducing a reduction of serum cytokine levels in all ravuconazole-treated mice. Our findings demonstrate that amlodipine is efficacious in enhancing the antiparasitic activity of ravuconazole in an experimental model of infection and indicates a potential strategy to be explored in Chagas disease treatment.
Topics: Amlodipine; Animals; Chagas Disease; Mice; Nitroimidazoles; Parasitemia; Thiazoles; Triazoles; Trypanocidal Agents; Trypanosoma cruzi
PubMed: 32423960
DOI: 10.1128/AAC.02497-19 -
Combinatorial Chemistry & High... 2022Hypertension is one of the most important health problems in the world and irbesartan and amlodipine are used in combination in various dosages for the treatment of high...
BACKGROUND
Hypertension is one of the most important health problems in the world and irbesartan and amlodipine are used in combination in various dosages for the treatment of high blood pressure.
OBJECTIVE
The aim of this study is to develop a fast, easy, sensitive, accurate, and precise squarewave voltammetry method for simultaneous determination of irbesartan and amlodipine besylate from pharmaceutical formulations at a hanging mercury drop electrode.
METHODS
In the applied method, since both active substances gave a peak at different potentials, no interference occurred between them. In optimization studies, Britton-Robinson buffer of pH 8.0 was chosen, in which the most appropriate peak shape and maximum peak current were observed. At the same time, as a result of instrumental parameter optimization to obtain reproducible results, 6 mV for scan increment, 30 mV for pulse amplitude, and 50 Hz for frequency were found suitable.
RESULTS
As a result of the calibration studies of the optimized method, linear working ranges were determined as 1.00-13.08 μg mL-1 for irbesartan and 5.83-16.51 μg mL-1 for amlodipine besylate. Limit of detection and limit of quantitation values were respectively calculated as 0.63 and 1.00 μg mL-1 for irbesartan and 0.50 and 1.98 μg mL-1 for amlodipine besylate. The results of precision values (RSD) ranged from 0.67% to 2.31% for irbesartan and 0.65% to 1.49% for amlodipine besylate. Accuracy values were calculated as -0.15% to 1.63% for irbesartan and -0.07% to 3.78% for amlodipine besylate. The results obtained from the recovery studies ranged from 101.05% to 102.78% and from 98.88% to 102.20% for amlodipine besylate and irbesartan, respectively.
CONCLUSION
After the validation studies of the developed method were carried out, it was successfully applied to pharmaceutical formulations containing these active substances.
Topics: Amlodipine; Drug Compounding; Electrodes; Irbesartan; Mercury
PubMed: 33475067
DOI: 10.2174/1386207324666210121110819 -
Proceedings of the National Academy of... May 2022There is currently no effective treatment for pancreatic ductal adenocarcinoma (PDAC). While palliative chemotherapy offers a survival benefit to most patients, nearly...
There is currently no effective treatment for pancreatic ductal adenocarcinoma (PDAC). While palliative chemotherapy offers a survival benefit to most patients, nearly all will eventually progress on treatment and long-term survivability remains poor. Given the lack of subsequent line treatment options, in this study, we sought to identify novel strategies to prevent, delay, or overcome resistance to gemcitabine, one of the most widely used medications in PDAC. Using a combination of single-cell RNA sequencing and high-throughput proteomic analysis, we identified a subset of gemcitabine-resistant tumor cells enriched for calcium/calmodulin signaling. Pharmacologic inhibition of calcium-dependent calmodulin activation led to the rapid loss of drug-resistant phenotypes in vitro, which additional single-cell RNA sequencing identified was due to impaired activation of the RAS/ERK signaling pathway. Consistent with these observations, calcium chelation or depletion of calcium in the culture media also impaired ERK activation in gemcitabine-resistant cells, and restored therapeutic responses to gemcitabine in vitro. We observed similar results using calcium channel blockers (CCBs) such as amlodipine, which inhibited prosurvival ERK signaling in vitro and markedly enhanced therapeutic responses to gemcitabine in both orthotopic xenografts and transgenic models of PDAC. Combined, these results offer insight into a potential means of gemcitabine resistance and suggest that select CCBs may provide a clinical benefit to PDAC patients receiving gemcitabine-based chemotherapy.
Topics: Amlodipine; Animals; Antineoplastic Agents; Calcium Channel Blockers; Calmodulin; Deoxycytidine; Humans; Pancreatic Neoplasms; United States; Gemcitabine
PubMed: 35476525
DOI: 10.1073/pnas.2200143119 -
Photodermatology, Photoimmunology &... Sep 2021
Topics: Amlodipine; Child; Humans; Melanocytes; Telangiectasis
PubMed: 33742476
DOI: 10.1111/phpp.12678 -
The Medical Journal of Australia Jun 1994
Topics: Amlodipine; Gynecomastia; Humans; Male; Middle Aged
PubMed: 8208207
DOI: 10.5694/j.1326-5377.1994.tb125970.x -
Clinical and Experimental Hypertension... Nov 2021This study was to investigate whether long-term amlodipine-based combination therapy attenuates seasonal variation of office blood pressure (BP) in hypertensive...
This study was to investigate whether long-term amlodipine-based combination therapy attenuates seasonal variation of office blood pressure (BP) in hypertensive patients. The data of 206 patients recruited in the Nanchang site of CHIEF trial were retrospectively analyzed. All patients received an amlodipine-based therapy for three years after reaching target BP with a 12-week titration treatment. Among them, 106 patients received amlodipine plus amiloride/hydrochlorothiazide (AA group) and 100 received amlodipine plus telmisartan (AT group) therapies. These patients were followed up every three months . The difference between the highest and lowest values of outdoor temperature in each three months was calculated as the seasonal temperature difference (T-d) and seasonal BP difference was calculated in the similar way. BP control rates in each season were calculated. In the three years, the highest SBP and DBP values occurred in winter and the lowest values in summer. As a result, the BP control rate in summer was the highest and that in winter was the lowest, especially for SBP. Although T-d levels were similar during three following-up years, the seasonal SBP/DBP differences in 2011 were significantly lower than 2009 (10.03 ± 5.74/6.96 ± 3.72 vs 14.36 ± 8.19/9.78 ± 5.21 mmHg, < .05), suggesting seasonal variation in BP was obviously reduced. Meanwhile, similar change was observed in AA and AT groups. Besides lower BP effectively, long-term amlodipine-based combination therapy could alleviate the seasonal BP variation in high-risk hypertensive patients.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Humans; Hypertension; Retrospective Studies; Seasons; Treatment Outcome
PubMed: 34338579
DOI: 10.1080/10641963.2021.1960363 -
Organic & Biomolecular Chemistry Feb 2023Advancing with our project about the development of new antiparasitic agents, we have enzymatically synthesized a series of amides derived from amlodipine, a calcium...
Advancing with our project about the development of new antiparasitic agents, we have enzymatically synthesized a series of amides derived from amlodipine, a calcium channel blocker used as an antihypertensive drug. Through lipase-catalyzed acylation with different carboxylic acids, nineteen amlodipine derivatives were obtained, eighteen of which were new compounds. To optimize the reaction conditions, the influence of several reaction parameters was analyzed, finding different requisites for aliphatic carboxylic acids and phenylacetic acids. All synthesized compounds were evaluated as antiproliferative agents against , the etiological agent of American trypanosomiasis (Chagas' disease). Some of them showed significant activity against the amastigote form of , the clinically relevant form of the parasite. Among synthesized compounds, the derivatives of myristic and linolenic acids showed higher efficacy and lower cytotoxicity. These results added to the advantages shown by the enzymatic methodology, such as mild reaction conditions and low environmental impact, making this approach a valuable way to synthesize these amlodipine derivatives with an application as promising antiparasitic agents.
Topics: Humans; Trypanosoma cruzi; Amlodipine; Antiparasitic Agents; Acylation; Carboxylic Acids; Trypanocidal Agents; Chagas Disease
PubMed: 36722938
DOI: 10.1039/d2ob02271k -
MMW Fortschritte Der Medizin Aug 2023
Topics: Humans; Antihypertensive Agents; Indapamide; Amlodipine
PubMed: 37537471
DOI: 10.1007/s15006-023-2868-1