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Margarita SaizSatjes, Francisco Javier Martinez-Martin
Antihypertensive treatment of patients with diabetes should include those drugs with a positive effect on metabolic parameters. Most patients with diabetes require at least two antihypertensive agents. Combining a dihydropyridine calcium channel blocker with a renin-angiotensin-aldosterone system inhibitor is a rational approach. However, not all dihydropyridines are equal with respect to their effects on metabolic parameters. Thus, manidipine exerts a positive effect on insulin resistance. However, this effect has not been observed with amlodipine...
2018: Drugs in Context
Beatrice Mercorelli, Anna Luganini, Marta Celegato, Giorgio Palù, Giorgio Gribaudo, Arianna Loregian
Currently, there are no therapeutic alternatives to DNA polymerase inhibitors to treat human cytomegalovirus (HCMV) infections, a major threat for immunocompromised patients and pregnant women. Here, we explored the potential to repurpose manidipine dihydrochloride (MND), a calcium antagonist clinically approved to treat hypertension, as a new anti-HCMV agent. MND emerged in a previous drug repurposing screen to find early inhibitors of HCMV replication, and now we confirm that it inhibits in the low micromolar range the replication of different HCMV strains, including clinical isolates and viruses resistant to approved DNA polymerase inhibitors...
February 2018: Antiviral Research
Shouichi Hosaka, Yuji Tokunaga
The powder properties of two 1,4-dihydropyridine type compounds, manidipine dihydrochloride (Man) and benidipine hydrochloride (Ben), which possess similar physicochemical properties, were compared through thermal and mechanical analyses. Man and Ben were compressed with lactose monohydrate (Lac) and magnesium stearate (Mgst) at different compression forces. As an index, we focused on the onset temperatures of Lac dehydration during thermal analysis and plotted them against compression forces to evaluate the differences in powder properties between Man and Ben...
2017: Chemical & Pharmaceutical Bulletin
Benchawan Chamsai, Sontaya Limmatvapirat, Srisagul Sungthongjeen, Pornsak Sriamornsak
CONTEXT: Low bioavailability of oral manidipine (MDP) is due to its low water solubility. OBJECTIVE: The objective of this study was to increase the solubility and bioavailability of MDP by fabricating ternary solid dispersion (tSD) with d-α-tocopherol polyethyleneglycol-1000-succinate and copovidone. METHODS: In this study, solid ternary phase diagram was applied in order to check the homogeneity of tSD prepared by melting and solidifying with dry ice...
December 2017: Drug Development and Industrial Pharmacy
Shaobo Wang, Yang Liu, Jiao Guo, Peilin Wang, Leike Zhang, Gengfu Xiao, Wei Wang
Japanese encephalitis virus (JEV), an arthropod-borne flavivirus, is a major cause of acute viral encephalitis in humans. No approved drug is available for the specific treatment of JEV infections, and the available vaccines are not effective against all clinical JEV isolates. In the study described here, a high-throughput screening of an FDA-approved drug library for inhibitors of JEV was performed. Five hit drugs that inhibited JEV infection with a selective index of >10 were identified. The antiviral activities of these five hit drugs against other flavivirus, including Zika virus, were also validated...
November 1, 2017: Journal of Virology
Vinayender Adireddy, Bhavani Prasanna Kumar Bimireddy, Venkateswarlu Ponneri
A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and validated for the enantioselective determination of manidipine in human plasma using isotope-labeled compounds as internal standards. After solid-phase extraction, R-(-)-manidipine and S-(+)-manidipine were chromatographed on a Chiralpack IC-3 C18 column using a isocratic mobile phase composed of 2 mm ammonium bicarbonate and acetonitrile (15:85, v/v). The precursor ion to product ion transitions for the enantiomers and internal standards were monitored in the multiple reaction monitoring and positive ionization mode using an API-4000 mass spectrometer...
December 2017: Biomedical Chromatography: BMC
Alberto Montanari, Davide Lazzeroni, Giovanna Pelà, Antonio Crocamo, Yuliya Lytvyn, Luisa Musiari, Aderville Cabassi, David Z I Cherney
Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 μg·kg(-1)·min(-1) N(G)-nitro-l-arginine methyl ester (l-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-isoprostane (U8-iso-PGF2αV; an oxidative stress marker) were measured...
May 1, 2017: American Journal of Physiology. Renal Physiology
Luca Monaco, Mauro Melis, Chiara Biagi, Monia Donati, Ester Sapigni, Alberto Vaccheri, Domenico Motola
BACKGROUND: In July 2012 a new European legislation (Directive 2010/84/EU and Regulation No. 1235/2010) regarding pharmacovigilance has become effective. It has boosted the activity of Signal Detection through a monthly analysis of potential safety signals on EudraVigilance (EV). Our aim is to describe the procedure of signal detection on EV data and to present results obtained by the our pharmacovigilance centre. METHOD: Data are extracted from EV database, which collects suspected Adverse Drug Reactions (ADRs) of medicinal products in Europe...
March 2017: Expert Opinion on Drug Safety
Margarita Saiz-Satjes, Francisco Javier Martinez-Martin, Alex Roca-Cusachs
AIMS: In AMANDHA trial, the addition of manidipine, but not amlodipine, in diabetic patients with uncontrolled hypertension, microalbuminuria and preserved renal function resulted in a large decrease of urinary albumin excretion (UAE) despite similar blood pressure (BP) reductions. Factors associated with the reduction of UAE were analyzed. METHODS: For this purpose, a multivariable analysis was performed. RESULTS: Although after 6 months of treatment, manidipine and amlodipine decreased BP to a similar extent, reductions of UAE were higher with manidipine...
March 2017: Future Cardiology
Benchawan Chamsai, Sontaya Limmatvapirat, Srisagul Sungthongjeen, Pornsak Sriamornsak
CONTEXT: Manidipine (MDP) is generally used clinically as an antihypertensive agent; however, the bioavailability of orally administered MDP is limited due to their very low water solubility. OBJECTIVE: The objectives of this research were, therefore, to increase the solubility of MDP by the formation of ternary solid dispersions (tSD) with polyethylene glycol 4000 (PEG4000) and copovidone and to improve their stability. METHODS: Solid ternary phase diagram was constructed to find homogeneous solid dispersion region after melting and solidifying at low temperature with different quenching substances...
March 2017: Drug Development and Industrial Pharmacy
Niloy Bhattacharjee, Sujata Barma, Nandita Konwar, Saikat Dewanjee, Prasenjit Manna
Diabetic nephropathy (DN), a chronic complication of diabetes, is charecterized by glomerular hypertrophy, proteinuria, decreased glomerular filtration, and renal fibrosis resulting in the loss of renal function. Although the exact cause of DN remains unclear, several mechanisms have been postulated, such as hyperglycemia-induced renal hyper filtration and renal injury, AGEs-induced increased oxidative stress, activated PKC-induced increased production of cytokines, chemokines, and different inflammatory and apoptotic signals...
November 15, 2016: European Journal of Pharmacology
Margarita Saiz Satjes, Francisco J Martinez-Martin
Renin-angiotensin system inhibitors should be considered as the first-line therapy in the treatment of patients with hypertension and diabetes. However, most of the diabetic subjects with hypertension require at least two drugs to achieve blood pressure targets. The ACCOMPLISH trial suggested that the best combination in the treatment of high-risk hypertensive patients should include a renin-angiotensin system inhibitor and a dihydropyridine. However, not all dihydropyridines block the same receptors. Those dihydropyridines that block T-type calcium channel blockers may provide additional advantages...
July 2016: Future Cardiology
Papapit Tuchinda, Kanokvalai Kulthanan, Sakunee Khankham, Kowit Jongjarearnprasert, Naruemon Dhana
BACKGROUND: Previous studies have shown that calcium channel blockers can cause cutaneous adverse reactions; however, the amounts of data collected are limited. Recently, there have been new drugs available for which only a few reports have been published with regard to cutaneous adverse reactions. OBJECTIVE: The purpose of our study was to estimate the rate and to study clinical patterns of cutaneous adverse drug reactions to calcium channel blockers. METHODS: Medical records of patients who had cutaneous adverse reactions to calcium channel blockers between January 2004 and December 2010, at the Adverse Drug Reaction Center of Siriraj hospital, Mahidol University, Bangkok, Thailand were reviewed...
September 2014: Asian Pacific Journal of Allergy and Immunology
Christos V Rizos, Moses S Elisaf
Hypertension plays a major role in the development and progression of micro- and macrovascular disease. Moreover, increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance. As a result the need for a comprehensive management of hypertensive patients is critical. However, the various antihypertensive drug categories have different effects on glucose metabolism. Indeed, angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis...
July 26, 2014: World Journal of Cardiology
Annalisa Zoppi, Amedeo Mugellini, Paola Preti, Andrea Rinaldi, Aldo Celentano, Emma Arezzi, Marco Alberici, Roberto Fogari
BACKGROUND: Failure to achieve good blood pressure (BP) control is probably the most important reason for high rates of morbidity and mortality in patients with hypertension. Combination therapy has been shown to increase the percentage of patients in whom BP control is achieved. One combination is a calcium channel blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I). OBJECTIVE: The aim of this study was to assess the effects of the fixed combination of the CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients already given monotherapy with either component but with poor results (ie, insufficient BP control or adverse events [AEs])...
July 2003: Current Therapeutic Research, Clinical and Experimental
Vítor Todeschini, Maximiliano da Silva Sangoi, Alianise da Silva Meira, Diogo Miron, Alini Dall Cortivo Lange, Nadia Maria Volpato
A stability-indicating micellar electrokinetic chromatography (MEKC) method was developed and validated for simultaneous analysis of delapril (DEL) and manidipine (MAN) using salicylic acid as an internal standard. The MEKC method was performed using a fused-silica capillary (effective length of 72 cm) with 50 mM of borate buffer and 5 mM of anionic surfactant sodium dodecylsulfate at pH 9.0 as the background electrolyte. The separation was achieved at 25 kV applied voltage and 35 degrees C. The injection was performed at 50 mbar for 5 s, with detection at 208 nm...
January 2014: Journal of AOAC International
Fernanda Malaquias Barboza, Willian Moreira Machado, Luiz Renato Olchanheski Junior, Josiane Padilha de Paula, Sônia Faria Zawadzki, Daniel Fernandes, Paulo Vitor Farago
Microparticles of poly(ε-caprolactone) (PCL) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) containing manidipine dihydrochloride (MAN) were successfully prepared by the simple emulsion/solvent evaporation method. All formulations showed loading efficiency rates greater than 80% and average particle size less than 8 μm. Formulations had spherical shape with smooth and porous surface for PCL and PHBV, respectively. According to Fourier-transform infrared spectroscopy, initial components were not chemically modified during microencapsulation...
2014: TheScientificWorldJournal
Vítor Todeschini, Amanda Thomas Barden, Leticia Lenz Sfair, Maximiliano da Silva Sangoi, Nadia Maria Volpato
A first-order derivative spectrophotometric (1D-UV) method was developed and validated for simultaneous determination of delapril (DEL) and manidipine (MAN) in tablets. The 1D-UV spectra were obtained using change lambda = 4.0 nm and wavelength set at 228 nm for DEL and 246 nm for MAN. The method was validated in accordance with the ICH requirements, involving the specificity, linearity, precision, accuracy, robustness and limits of detection and quantitation. The method showed high specificity in the presence of two drugs and formulation excipients and was linear over the concentration range of 18-54 microg mL(-1) (r2 = 0...
2013: Acta Chimica Slovenica
Loreley Betancourt-Castellanos, Esther Ponz-Clemente, M Sol Otero-López, Conchita Blasco-Cabañas, Dolors Marquina-Parra, Manuel García-García
Turbid acellular peritoneal fluid of a non-infectious aetiology is an uncommon entity in peritoneal dialysis and is characterised by a high concentration of triglycerides in the peritoneal fluid. The most common causes include cancer, lymphatic obstructions, pancreatitis, trauma, and even the use of certain medications such as calcium antagonists. The largest studies concerning this entity have been carried out in patients of Asian descent. We recently diagnosed 4 cases of turbid acellular peritoneal fluid at our institution in relation to the use of calcium antagonists...
2013: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
A J García Ruiz, J A Divisón Garrote, N García-Agua Soler, F Morata García de la Puerta, A C Montesinos Gálvez, L Avila Lachica
OBJECTIVE: The aim of this study is to compare the efficiency of different fixed-dose combinations of renin-angiotensin-aldosterone system (RAAS) blockers and calcium channel blockers, to use it as a guide to assist the rational prescribing in antihypertensive therapy. METHODS: The efficacy of each drug was obtained from intervention studies randomized, double-blind, made with these combinations and a utility-cost modeling from the model proposed and used by NICE...
March 2013: Semergen
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