Therapeutic effectiveness
Dinesh Kumar Jain in Homeopathy, 2022
Now we should know how much time will be taken by a drug for its development? And what types of studies are required before successful development of a drug or treatment? Initial safety, biological effects, receptor study, enzyme inhibition and selectivity, drug absorption, metabolism, excretion, therapeutic efficacy, dose range, kinetics and adverse reaction, acute, subacute, chronic studies, effect on reproductive behavior, carcinogenic potential, mutagenic potential are studied and analyzed by clinical pharmacologist and physicians. Most new drug candidates are identified through chemical modification of known molecules, screening of natural products or previously discovered chemical entities for biological activity or rational drug design based on an understanding of biological mechanisms. Average ten years are taken by a drug before marketing and even after marketing surveillance is continued. If new toxicity appears after marketing, the drug is withdrawn from the market and the whole exercise of drug development becomes useless.
Drugs in pregnancy and lactation
Evelyne Jacqz-Aigrain, Imti Choonara in Paediatric Clinical Pharmacology, 2021
Safety evaluation programs include two relevant species in which the compound is pharmacologically active for detection of the embryo-fetal toxicity studies; one rodent and one non-rodent species are requested. Due to the placental similarities between humans and rodents or rabbits, the majority of the regulatory embryo-fetal toxicity studies are routinely performed in the rat and rabbit. The biological activity with species and/or tissue specificity of compounds should be considered. Some are biologically active in conventional toxicity species, while others have species-specific biological activity. Non-human primates are rarely used as alternative test species, since historical data are poor and the rate of spontaneous anomalies is often high. However, for biotechnology products when only one species can be identified or where the biological activity of the product is well understood, one relevant species may suffice. Toxicity studies in non-relevant species may be misleading and are discouraged.
Pharmogenology: The Industrial New Drug Development Process
Gary M. Matoren in The Clinical Research Process in the Pharmaceutical Industry, 2020
The specific tests performed in isolated tissues, organ systems, or in whole animals are, of course, a direct reflection of the pharmaceutical company's therapeutic goals as earlier delineated. This is a most important concept which often eludes the uninitiated. The discovery of interesting and possibly therapeutically significant biological activity is a summation and evaluation of selected studies or tests done in the departments of microbiology, biochemistry, endocrinology, and pharmacology. These studies, tests, and screens are established to determine whether the molecules synthesized by the medicinal chemist have activity that will make them of interest for further study or for chemical synthetic analoging. However, this information is, of necessity, restricted by the nature of the biological tests, and these tests are restricted to the expressed areas of therapeutic interests and capabilities of the individual pharmaceutical company.
Promising strategies for improving oral bioavailability of poor water-soluble drugs
Published in Expert Opinion on Drug Discovery, 2023
Bruna Rocha, Letícia Aparecida de Morais, Mateus Costa Viana, Guilherme Carneiro
Numerous strategies can be found in the literature to improve poorly water-soluble drugs using conventional or novel methods. Conventional strategies involve drug molecular and crystal structure alterations, forming prodrugs, salts, ionic pairs, coamorphous systems, and cocrystals. The main objective of these strategies is to increase the aqueous solubility of drugs and not necessarily bypass the barriers of the gastrointestinal environment, first-pass metabolism, or even increase intestinal absorption. Hence, few studies involving these strategies have analyzed the effective increase in bioavailability, although several have achieved effective gains in biological activity. The alterations in conventional solid dosage forms are usually altered tablets to better carry the drug through the GIT and increase its absorption by increasing the gastrointestinal residence time, which includes the mucoadhesive and floating systems. Orodispersive films and amorphous solid dispersions have also been proposed to increase the bioavailability of these poorly water-soluble drugs. Some of these strategies already have more established use in the literature and shown to improve water-solubility, dissolution rate, absorption extension, and drug bioavailability.
Advances in computer-aided drug design for type 2 diabetes
Published in Expert Opinion on Drug Discovery, 2022
Wanqiu Huang, Luyong Zhang, Zheng Li
PPARs (including PPARα, PPARδ, and PPARγ) belong to the nuclear hormone receptor superfamily [51], which play a pivotal role in energy homeostasis, and are considered an important target in the treatment of diabetes [52]. Maltarollo et al. [53] performed a structure-based virtual screening to explore new agonists of PPARδ, which led to the identification of five hits. Among them, four compounds showed good bioactivity in preliminary in vitro tests. In this study, 740,000 compounds from ZINC database were docked with PPARδ, in which the binding energy and visual inspections were used to rank compounds, and 50 compounds were screened out. Then, the 50 compounds were re-docked in the PPARδ active site, and five potential PPAR affinity substances were selected for further biological assays. Compounds 1 and 2 had PPARδ/γ activity. Compound 3 showed PPARγ activity and compound 4 was a PPARδ agonist (Figure 2). This research also found that the tetrazole group could be used as the bioisosteres of the acid moiety presenting in typical PPAR ligands.
Safety and biological activity evaluation of Uncaria rhynchophylla ethanolic extract
Published in Drug and Chemical Toxicology, 2022
Heung Bin Lim, Hyeong Ryeol Lee
Secondary metabolites are some of the most abundant sources of potential drugs. Natural products contain a number of indicator compounds that exhibit biological activity. Research into the development of new materials using natural products with a lower economic burden, lower side effects, and excellent biological activity is attracting attention (Newman and Cragg 2007). Therefore, studies are being actively conducted to search for new active substances derived from natural products (Namdeo 2007). Among natural products, plants are a major source of secondary metabolites that exhibit antimutagenic and anticancer activities. There are also strong correlations between antimutagenic and antioxidative activities in several studies, and it has been reported that phenolic compounds are attributed to such activities (Santos-Cervantes et al. 2007, Zahin, Ahmad, et al. 2010, Zahin, Aqil, et al. 2010, Zahin et al. 2013).
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