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Alcoholism, Clinical and Experimental... Mar 2015Annually, the use and abuse of alcohol contributes to millions of deaths and billions of dollars in societal costs. To determine the impact of genetic variation on the... (Review)
Review
BACKGROUND
Annually, the use and abuse of alcohol contributes to millions of deaths and billions of dollars in societal costs. To determine the impact of genetic variation on the susceptibility to the disorder and its response to treatment, studies have been conducted to assess the contribution of a variety of candidate genetic variants. These variants, which we review here, were chosen based upon their observed or hypothesized functional relevance to alcohol use disorder (AUD) risk or to the mechanism by which medications used to treat the disorder exert their effects.
METHODS
This qualitative review examines studies in which candidate polymorphisms were tested as moderator variables to identify pharmacogenetic effects on either the subjective response to alcohol or the outcomes of pharmacotherapy.
RESULTS
Although findings from these studies provide evidence of a number of clinically relevant pharmacogenetic effects, the literature is limited and there are conflicting findings that require resolution.
CONCLUSIONS
Pharmacogenetic studies of AUD treatment that use greater methodological rigor and better statistical controls, such as corrections for multiple testing, may help to resolve inconsistent findings. These procedures could also lead to the discovery of more robust and clinically meaningful moderator effects. As the field evolves through methodological standardization and the use of larger study samples, pharmacogenetic research has the potential to inform clinical care by enhancing therapeutic effects and personalizing treatments. These efforts may also provide insights into the mechanisms by which medications reduce heavy drinking or promote abstinence in patients with an AUD.
Topics: Alcohol-Related Disorders; Genetic Variation; Humans; Pharmacogenetics; Randomized Controlled Trials as Topic
PubMed: 25703505
DOI: 10.1111/acer.12643 -
Marine Drugs Feb 2016Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea... (Review)
Review
Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.
Topics: Animals; Aquatic Organisms; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Drug Design; Gene Transfer Techniques; Humans; Oceans and Seas; Polysaccharides; Regenerative Medicine
PubMed: 26861358
DOI: 10.3390/md14020034 -
Trends in Pharmacological Sciences Mar 2013Pharmaceutical co-crystal formation represents a straightforward way to dramatically influence the solid-state properties of a drug substance, particularly its... (Review)
Review
Pharmaceutical co-crystal formation represents a straightforward way to dramatically influence the solid-state properties of a drug substance, particularly its solubility and hence bioavailability. This short review summarises this highly topical field, covering why the topic is of interest in pharmaceutical formulation, the definitions and practical scope of co-crystals, co-crystal preparation and characterisation, and implications for regulatory control and intellectual property (IP) protection. Concepts are illustrated with highly selected examples of pharmaceutical co-crystal systems within the wider context of crystal engineering and research in molecular solids.
Topics: Chemistry, Pharmaceutical; Crystallization; Drug Design; Humans; Pharmaceutical Preparations
PubMed: 23347591
DOI: 10.1016/j.tips.2012.12.003 -
Sports Medicine (Auckland, N.Z.) Apr 2019The World Anti-Doping Agency is responsible for maintaining a Prohibited List that describes the use of substances and methods that are prohibited for athletes. The list... (Review)
Review
The World Anti-Doping Agency is responsible for maintaining a Prohibited List that describes the use of substances and methods that are prohibited for athletes. The list currently contains 23 substance classes, and an important reason for the existence of this list is to prevent unfair competition due to pharmacologically enhanced performance. The aim of this review was to give an overview of the available evidence for performance enhancement of these substance classes. We searched the scientific literature through PubMed for studies and reviews evaluating the effects of substance classes on performance. Findings from double-blind, randomized controlled trials were considered as evidence for (the absence of) effects if they were performed in trained subjects measuring relevant performance outcomes. Only 5 of 23 substance classes show evidence of having the ability to enhance actual sports performance, i.e. anabolic agents, β2-agonists, stimulants, glucocorticoids and β-blockers. One additional class, growth hormone, has similar evidence but only in untrained subjects. The observed effects all relate to strength or sprint performance (and accuracy for β-blockers); there are no studies showing positive effects on reliable markers of endurance performance. For 11 classes, no well-designed studies are available, and, for the remaining six classes, there is evidence of an absence of a positive effect. In conclusion, for the majority of substance classes, no convincing evidence for performance enhancement is available, while, for the remaining classes, the evidence is based on a total of only 266 subjects from 11 studies.
Topics: Adrenergic beta-Antagonists; Anabolic Agents; Athletic Performance; Central Nervous System Stimulants; Doping in Sports; Evidence-Based Practice; Human Growth Hormone; Humans; Intercellular Signaling Peptides and Proteins; Peptide Hormones; Performance-Enhancing Substances; Randomized Controlled Trials as Topic; Steroids
PubMed: 30411235
DOI: 10.1007/s40279-018-1014-1 -
Polimery W Medycynie 2018Polymorphism of pharmaceutical substances has a significant impact on their physicochemical properties, durability, bioavailability and consequently on their... (Review)
Review
Polymorphism of pharmaceutical substances has a significant impact on their physicochemical properties, durability, bioavailability and consequently on their pharmacological activity. Solid dosage forms may exist in both crystalline and amorphous forms. Amorphous varieties are characterized by higher solubility and dissolution rates, while crystalline forms show greater purity and storage stability. The choice between the crystalline or amorphous form of a drug is extremely important to ensure effective and safe pharmacotherapy. Statins - the most commonly used group of drugs in the treatment of lipid disorders - are an example of drugs that occur in many crystalline and amorphous forms. Statins belong to class II in the biopharmaceutical classification system (BCS), which means that they are poorly soluble, but permeate biological membranes well. The bioavailability of statins shows considerable variation, which is associated with the first-pass effect in the liver and the accumulation of the drug in the hepatocytes. The improvement of bioavailability after oral administration of poorly soluble medicinal substances remains one of the most challenging aspects of the drug development process. A specific polymorphic form is obtained by applying appropriate conditions during the process of its preparation under industrial conditions, including the use of a suitable solvent, a specific temperature or rate of crystallization. The article provides a comprehensive update on the current knowledge of the influence of polymorphic form on statin solubility and bioavailability. Research is still being carried out to obtain new polymorphic varieties of statins that are characterized by better physicochemical and pharmacokinetic parameters.
Topics: Biological Availability; Chemistry, Pharmaceutical; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmaceutical Preparations; Solubility
PubMed: 30916495
DOI: 10.17219/pim/102978 -
Cells May 2019Angiogenesis inhibitors (AIs) have become established as an effective cancer treatment. Whereas their interactions with antineoplastic drugs have extensively been... (Review)
Review
Angiogenesis inhibitors (AIs) have become established as an effective cancer treatment. Whereas their interactions with antineoplastic drugs have extensively been investigated, little is known of the effect of their co-administration with nutraceuticals/dietary supplements (N/DSs), which are often self-prescribed. N/DSs comprise a wide range of products such as herbs, nutrients, vitamins, minerals, and probiotics. Assessment of their interactions with cancer drugs, particularly AIs, is hampered by the difficulty of gauging the amount of active substances patients actually take. Moreover, there is no agreement on which approach should be used to determine which N/DSs are most likely to influence AI treatment efficacy. We present a comprehensive review of the metabolic routes of the major AIs and their possible interactions with N/DSs. The PubMed and Cochrane databases were searched for papers describing the metabolic routes of the main AIs and N/DSs. Data from the 133 studies thus identified were used to compile a diagnostic table reporting known and expected AI-N/DS interactions based on their metabolization pathways. AIs and N/DSs sharing the cytochrome P450 pathway are at risk of negative interactions. Recent advances in pharmacogenetics offer exceptional opportunities to identify prognostic and predictive markers to enhance the efficacy of individualized AI treatments. The table provides a guide to genotyping patients who are due to receive AIs and is a promising tool to prevent occult AI-N/DS interactions in poor metabolizers. N/DS use by cancer patients receiving AIs is a topical problem requiring urgent attention from the scientific community.
Topics: Angiogenesis Inhibitors; Animals; Dietary Supplements; Drug Interactions; Humans; Neovascularization, Pathologic; Pharmacogenetics; Vascular Endothelial Growth Factor A
PubMed: 31151284
DOI: 10.3390/cells8060522 -
Addiction pharmacogenetics: a systematic review of the genetic variation of the dopaminergic system.Psychiatric Genetics Oct 2015Substance use disorders have significant personal, familial, and societal consequences. Despite the serious consequences of substance use, only a few therapies are... (Review)
Review
Substance use disorders have significant personal, familial, and societal consequences. Despite the serious consequences of substance use, only a few therapies are effective in treating substance use disorders, thus highlighting a need for improved treatment practices. Substance use treatment response depends on multiple factors such as genetic, biological, and social factors. It is essential that each component is represented in treatment plans. The dopaminergic system plays a critical role in the pharmacotherapy for addictions, and an understanding of the role of variation of genes involved in this system is essential for its success. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement guidelines. A computerized literature search was conducted using PubMed and Scopus (all databases). Articles published up to April 2015 that examined the role of dopaminergic gene variation in the pharmacotherapy of alcohol, opioid, and cocaine use disorders were reviewed. Search terms were dopamine, gene, polymorphism, substance abuse, treatment, and response. Polymorphisms of the DRD2, ANKK1, DAT1, DBH, and DRD4 genes have been found to moderate the effects of pharmacotherapy of alcohol, opioid, and cocaine use disorders. The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders. More studies are needed to confirm and extend these findings.
Topics: Dopamine; Genetic Predisposition to Disease; Humans; Pharmacogenetics; Polymorphism, Genetic; Precision Medicine; Substance-Related Disorders
PubMed: 26146874
DOI: 10.1097/YPG.0000000000000095 -
International Journal of Molecular... Feb 2019This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion... (Review)
Review
This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion complexes with cyclodextrins and their biological studies in vitro and in vivo; (ii) Evaluation and comparison of the bioactive efficacy of complexed and non-complexed substances; (iii) Chemical and biological performance tests of inclusion complexes, aimed at the development of new pharmaceutical products. Based on the evidence presented in the review, it is clear that cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability. Although the literature shows the importance of their ability to help produce innovative biotechnological substances, we still need more studies to develop and expand their therapeutic properties. It is, therefore, very important to gather together evidence of the effectiveness of inclusion complexes with cyclodextrins in order to facilitate a better understanding of research on this topic and encourage further studies.
Topics: Animals; Chemistry, Pharmaceutical; Cyclodextrins; Drug Evaluation, Preclinical; Humans; Structure-Activity Relationship; Technology, Pharmaceutical
PubMed: 30717337
DOI: 10.3390/ijms20030642 -
The AAPS Journal Jan 2022The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the... (Review)
Review
The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the use of excipients in drug products for decades, considerable research efforts have been directed towards evaluating their potential effects on drug bioavailability. Potential excipient concerns stem from drug formulation changes (e.g., scale-up and post-approval changes, development of a new generic product). Regulatory agencies have established in vivo bioequivalence standards and, as a result, may waive the in vivo requirement, known as a biowaiver, for some oral products. Biowaiver acceptance criteria are based on the in vitro characterization of the drug substance and drug product using the Biopharmaceutics Classification System (BCS). Various regulatory guidance documents have been issued regarding BCS-based biowaivers, such that the current FDA guidance is more restrictive than prior guidance, specifically about excipient risk. In particular, sugar alcohols have been identified as potential absorption-modifying excipients. These biowaivers and excipient risks are discussed here. Graphical Abstract.
Topics: Animals; Biological Availability; Biopharmaceutics; Drug Compounding; Drug Development; Drug and Narcotic Control; Excipients; Humans; Permeability; Pharmaceutical Preparations; Therapeutic Equivalency
PubMed: 34988701
DOI: 10.1208/s12248-021-00670-1