China
Africa
Explore chapters and articles related to this topic
The Evolution of Anticancer Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Various methodologies exist or have been developed to identify suitable drug candidates for Repurposing. For example, phenotypic drug-screening methods often discover drug candidates accidentally, with new pharmacological activities identified based on an unexpected signal from in vitro or in vivo models, or sometimes from clinical observations (e.g., sildenafil). Robotic screening platforms and highly sensitive detection systems have been developed that allow the rapid screening of large chemical libraries, including libraries of existing approved therapeutic agents (e.g., the commercially available SelleckChem library of 2,572 FDA-approved drugs (https://www.selleckchem.com/screening/fda-approved-drug-library.html) or the ReFRAME collection of 12,000 compounds for the academic and nonprofit research community which contains small molecules that have reached clinical development or undergone significant preclinical profiling (doi: 10.1073/pnas.1810137115). In the oncology area, phenotypic screening has been used to identify FDA-approved calcium channel blockers as potent inhibitors of filopodia formation in cancer cells. In these studies, the importance of l-type calcium channels in regulating calcium entry and filopodia stabilization was observed by treating cancer cells expressing MYO10-GEP with a library of compounds, including l-type calcium channel blockers such as amlodipine, felodipine, manidipine, and cilnidipine. It was found that these agents were able to inhibit filopodia formation and block cancer cell invasion.
Dual-drug amorphous formulation of gliclazide
Published in Drug Development and Industrial Pharmacy, 2021
Marwah Aljohani, Patrick McArdle, Andrea Erxleben
Coamorphization with a small-molecule coformer is well-documented in the literature as a strategy to enhance the dissolution properties and thus the bioavailability of poorly water-soluble drugs [1–3]. Various types of biocompatible, inactive small-molecule coformers have been successfully studied such as amino acids [4–7], carboxylic acids [8–11], sugars [12], nicotinamide [13], saccharin [14,15], and bile acids [16,17]. The coformer stabilizes the amorphous phase through intermolecular interactions with the drug molecules and/or by providing a physical barrier to recrystallization. In addition to drug-excipient combinations, drug-drug coamorphous systems in which the inactive coformer is replaced by a second complementary drug have been described and highlighted in the literature as a new perspective for fixed-dose combination therapeutics [18,19]. The first dual-drug coamorphous system was reported by Yamamura et al. who showed that coamorphization of cimetidine and naproxen enhanced the stability of the amorphous form of both drugs, resulting in an improved solubility and dissolution rate [20,21]. Lodagekar et al. reported a stable coamorphous system of two antihypertensive drugs, valsartan and cilnidipine. At the therapeutically relevant dose ratio of 16:1 the release of cilnidipine was significantly enhanced [22]. Other examples include the combination of cimetidine and diflunisal [23], indomethacin and naproxen [24], simvastatin and glipizide [25], ritonavir and indomethacin [26], nateglinide and metformin hydrochloride [27], omeprazole and amoxicillin trihydrate [28] and tranilast and diphenhydramine [29].
Cilnidipine loaded poly (ε-caprolactone) nanoparticles for enhanced oral delivery: optimization using DoE, physical characterization, pharmacokinetic, and pharmacodynamic evaluation
Published in Pharmaceutical Development and Technology, 2021
Rimpy Diwan, Punna Rao Ravi, Shubham Ishwar Agarwal, Vidushi Aggarwal
Cilnidipine (CND) is a dihydropyridine calcium antagonist used in the treatment of hypertension and other cardiovascular disorders (Uneyama et al. 2006). CND possesses poor aqueous solubility and a limited dissolution rate. It has good intestinal permeability due to its hydrophobic nature (log P value 4.7). CND is reported to have poor oral bioavailability (∼13%) in humans (Uesawa and Mohri 2008) due to its poor aqueous solubility and limited dissolution rate. In addition, CND is highly metabolized in the liver due to the first-pass effect (Liu et al. 2003). Although CND possesses poor oral absorption properties, it is one of the highly prescribed anti-hypertensive drugs due to its efficacy and safety profile compared to other calcium channel blockers (Shete 2016).
A post-marketing survey evaluating the safety and efficacy of a fixed-dose single-pill combination of cilnidipine and valsartan in patients with hypertension: Real-world JSH 2014 and 2019 implementations
Published in Clinical and Experimental Hypertension, 2020
Saori Matsuda, Shinobu Nagahama, Yoshiki Kurose, Maki Wakabayashi, Hitoshi Sugii, Tsukasa Teshima, Noriyuki Suzuki, Kazuomi Kario
The treatment regimen for any chronic disease should be simple to improve the likelihood of adherence to the prescribed medication. For the management of hypertension, the most common therapeutic strategy is the initiation of antihypertensive drug monotherapy to achieve optimal blood pressure (BP). However, to achieve a more potent BP lowering effect, a combination of antihypertensive drugs from different classes should be considered (1,2). Combining two or three antihypertensive drugs at a fixed dose in a single tablet helps to reduce the number of pills that needs to be taken daily, resulting in improved adherence, which is notably low in patients with hypertension (3,4). In addition, fixed-dose combination drugs also improve the rate of BP control (5,6). All recent European, American, and Asian hypertension guidelines recommend the use of an antihypertensive in the form of a fixed-dose, single-pill combination (SPC) when multidrug therapy is indicated (7–9). Cilnidipine, a calcium channel blocker, inhibits L-type and N-type calcium channels (10,11). Valsartan is an angiotensin II receptor blocker (12). ATEDIO® Combination Tablet, an SPC of cilnidipine 10 mg and valsartan 80 mg (SPC of Cil/Val), was approved by the Ministry of Health, Labor and Welfare of Japan in March 2014. However, the safety and efficacy of SPC of Cil/Val has not been evaluated in real-world settings. The home blood pressure (HBP) control by a single-pill combination of cilnidipine and valsartan (HOPE-Combi) survey aimed to assess the real-world safety and efficacy of the SPC of Cil/Val in patients with hypertension. Moreover, BP control was investigated according to the target BP level recommended in The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH) 2014 (1) or JSH 2019 (2).