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Marine Drugs Nov 2020Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has... (Review)
Review
Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has attracted increasing interest in recent decades due to its effective and potential contribution to the selection of rational dosage recommendations and the optimal use of the therapeutic arsenal. In general, pharmacokinetics studies how drugs change after administration via the processes of absorption, distribution, metabolism, and excretion (ADME). This review provides a summary of the pharmacokinetics studies of marine-derived active compounds, with a particular focus on their ADME. The pharmacokinetics of compounds derived from algae, crustaceans, sea cucumber, fungus, sea urchins, sponges, mollusks, tunicate, and bryozoan is discussed, and the pharmacokinetics data in human experiments are analyzed. In-depth characterization using pharmacokinetics is useful for obtaining information for understanding the molecular basis of pharmacological activity, for correct doses and treatment schemes selection, and for more effective drug application. Thus, an increase in pharmacokinetic research on marine-derived compounds is expected in the near future.
Topics: Animals; Aquatic Organisms; Biological Availability; Biological Products; Drug Dosage Calculations; Half-Life; Humans; Metabolic Clearance Rate; Tissue Distribution
PubMed: 33182407
DOI: 10.3390/md18110557 -
The American Journal of Clinical... May 2004Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases such as cancer and cardiovascular diseases is... (Review)
Review
Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases such as cancer and cardiovascular diseases is emerging. The health effects of polyphenols depend on the amount consumed and on their bioavailability. In this article, the nature and contents of the various polyphenols present in food sources and the influence of agricultural practices and industrial processes are reviewed. Estimates of dietary intakes are given for each class of polyphenols. The bioavailability of polyphenols is also reviewed, with particular focus on intestinal absorption and the influence of chemical structure (eg, glycosylation, esterification, and polymerization), food matrix, and excretion back into the intestinal lumen. Information on the role of microflora in the catabolism of polyphenols and the production of some active metabolites is presented. Mechanisms of intestinal and hepatic conjugation (methylation, glucuronidation, sulfation), plasma transport, and elimination in bile and urine are also described. Pharmacokinetic data for the various polyphenols are compared. Studies on the identification of circulating metabolites, cellular uptake, intracellular metabolism with possible deconjugation, biological properties of the conjugated metabolites, and specific accumulation in some target tissues are discussed. Finally, bioavailability appears to differ greatly between the various polyphenols, and the most abundant polyphenols in our diet are not necessarily those that have the best bioavailability profile. A thorough knowledge of the bioavailability of the hundreds of dietary polyphenols will help us to identify those that are most likely to exert protective health effects.
Topics: Biological Availability; Flavonoids; Food Analysis; Humans; Intestinal Absorption; Phenols; Polyphenols; Tissue Distribution
PubMed: 15113710
DOI: 10.1093/ajcn/79.5.727 -
British Journal of Clinical Pharmacology Mar 2015A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with... (Review)
Review
A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. Healthcare professionals need to be aware of anatomical and physiological changes that affect pharmacokinetic profiles of drugs to understand consequences of dose adjustments in infants and children. Pharmacokinetic clinical trials in children are complicated owing to the limitations on blood sample volumes and perception of pain in children resulting from blood sampling. There are alternative sampling techniques that can minimize the invasive nature of such trials. Population based models can also limit the sampling required from each individual by increasing the overall sample size to generate robust pharmacokinetic data. This review details key considerations in the design and development of paediatric pharmacokinetic clinical trials.
Topics: Child; Clinical Trials as Topic; Humans; Inactivation, Metabolic; Intestinal Absorption; Models, Biological; Pediatrics; Pharmaceutical Preparations; Pharmacokinetics; Tissue Distribution
PubMed: 25855821
DOI: 10.1111/bcp.12267 -
Nucleic Acids Research Jul 2021Because undesirable pharmacokinetics and toxicity of candidate compounds are the main reasons for the failure of drug development, it has been widely recognized that...
Because undesirable pharmacokinetics and toxicity of candidate compounds are the main reasons for the failure of drug development, it has been widely recognized that absorption, distribution, metabolism, excretion and toxicity (ADMET) should be evaluated as early as possible. In silico ADMET evaluation models have been developed as an additional tool to assist medicinal chemists in the design and optimization of leads. Here, we announced the release of ADMETlab 2.0, a completely redesigned version of the widely used AMDETlab web server for the predictions of pharmacokinetics and toxicity properties of chemicals, of which the supported ADMET-related endpoints are approximately twice the number of the endpoints in the previous version, including 17 physicochemical properties, 13 medicinal chemistry properties, 23 ADME properties, 27 toxicity endpoints and 8 toxicophore rules (751 substructures). A multi-task graph attention framework was employed to develop the robust and accurate models in ADMETlab 2.0. The batch computation module was provided in response to numerous requests from users, and the representation of the results was further optimized. The ADMETlab 2.0 server is freely available, without registration, at https://admetmesh.scbdd.com/.
Topics: Drug-Related Side Effects and Adverse Reactions; Internet; Pharmaceutical Preparations; Pharmacokinetics; Phthalazines; Piperazines; Software
PubMed: 33893803
DOI: 10.1093/nar/gkab255 -
European Journal of Pharmaceutical... Jun 2019The simultaneous intake of food and drugs can have a strong impact on drug release, absorption, distribution, metabolism and/or elimination and consequently, on the... (Review)
Review
The simultaneous intake of food and drugs can have a strong impact on drug release, absorption, distribution, metabolism and/or elimination and consequently, on the efficacy and safety of pharmacotherapy. As such, food-drug interactions are one of the main challenges in oral drug administration. Whereas pharmacokinetic (PK) food-drug interactions can have a variety of causes, pharmacodynamic (PD) food-drug interactions occur due to specific pharmacological interactions between a drug and particular drinks or food. In recent years, extensive efforts were made to elucidate the mechanisms that drive pharmacokinetic food-drug interactions. Their occurrence depends mainly on the properties of the drug substance, the formulation and a multitude of physiological factors. Every intake of food or drink changes the physiological conditions in the human gastrointestinal tract. Therefore, a precise understanding of how different foods and drinks affect the processes of drug absorption, distribution, metabolism and/or elimination as well as formulation performance is important in order to be able to predict and avoid such interactions. Furthermore, it must be considered that beverages such as milk, grapefruit juice and alcohol can also lead to specific food-drug interactions. In this regard, the growing use of food supplements and functional food requires urgent attention in oral pharmacotherapy. Recently, a new consortium in Understanding Gastrointestinal Absorption-related Processes (UNGAP) was established through COST, a funding organisation of the European Union supporting translational research across Europe. In this review of the UNGAP Working group "Food-Drug Interface", the different mechanisms that can lead to pharmacokinetic food-drug interactions are discussed and summarised from different expert perspectives.
Topics: Administration, Oral; Biological Availability; Drug Liberation; Europe; Food-Drug Interactions; Gastrointestinal Absorption; Gastrointestinal Tract; Humans; Intestinal Absorption; Pharmacokinetics
PubMed: 30974173
DOI: 10.1016/j.ejps.2019.04.003 -
British Journal of Clinical Pharmacology Jan 2004Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore,... (Review)
Review
Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiological stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.
Topics: Aging; Biological Availability; Digestive System; Heart; Humans; Kidney; Metabolic Clearance Rate; Neurosecretory Systems; Pharmacokinetics; Pharmacology; Protein Binding
PubMed: 14678335
DOI: 10.1046/j.1365-2125.2003.02007.x -
Journal of Clinical Pharmacology Feb 2020Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetic (PK) phenomenon that is caused by high-affinity binding of a compound to its... (Review)
Review
Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetic (PK) phenomenon that is caused by high-affinity binding of a compound to its pharmacologic targets. As the interaction between a drug and its pharmacologic target belongs to the process of pharmacodynamics (PD), TMDD can be viewed as a consequence of "PD affecting PK." Although there are numerous TMDD-related articles in the literature, most of them focus on characterizing TMDD using various mathematical models, which may not be suitable for those readers who have little interest in mathematical modeling and only want to have an understanding of the basic concept. The goal of this review is to serve as a "primer" on TMDD. This review explains (1) how TMDD happens; (2) why large-molecule and small-molecule compounds exhibiting TMDD demonstrate substantially different nonlinear PK behaviors; (3) what nonlinear PK profiles look like in large-molecule and small-molecule compounds exhibiting TMDD, using pegfilgrastim, erythropoietin, ABT-384, and linagliptin as case examples; and (4) how to identify whether the nonlinear PK of a compound is because of TMDD.
Topics: Animals; Drug Delivery Systems; Humans; Nonlinear Dynamics; Pharmaceutical Preparations; Pharmacokinetics; Tissue Distribution
PubMed: 31793004
DOI: 10.1002/jcph.1545 -
Annals of Nutrition & Metabolism 2008Food-drug interactions are defined as alterations of pharmacokinetics or pharmacodynamics of a drug or nutritional element or a compromise in nutritional status as a... (Review)
Review
Food-drug interactions are defined as alterations of pharmacokinetics or pharmacodynamics of a drug or nutritional element or a compromise in nutritional status as a result of the addition of a drug. Elderly patients are particularly at risk because more than 30% of all the prescription drugs are taken by this population. Failure to identify and properly manage drug-nutrient interactions can lead to serious consequences. For instance, drug-nutrient interactions can result in reduced absorption of certain oral antibiotics and may lead to suboptimal antibiotic concentrations at the site of infection. This predisposes the patient to treatment failure. Induction or inhibition of enzymes in the gut by nutrients may lead to a significant change in oral bioavailability of drugs or vice versa. For example, grapefruit juice is a selective intestinal CYP3A4 inhibitor. The overall exposure of some drugs can be increased by more than fivefold when taken with grapefruit juice and increase the risk of adverse effects. The use of certain drugs may affect GI tract function and may lead to a loss of bodily electrolytes and fluid. Limiting drug prescriptions to essential medications for as short a period as possible and periodic re-evaluations of the treatment chosen are essential to minimize adverse drug-nutrient interactions.
Topics: Aged; Aged, 80 and over; Biological Availability; Female; Food-Drug Interactions; Health Status; Humans; Intestinal Absorption; Male; Nutritional Status; Pharmaceutical Preparations; Pharmacokinetics
PubMed: 18382075
DOI: 10.1159/000115345 -
Clinical and Translational Science Nov 2018The tutorial introduces the readers to the fundamentals of antibody pharmacokinetics (PK) in the context of drug development. Topics covered include an overview of...
The tutorial introduces the readers to the fundamentals of antibody pharmacokinetics (PK) in the context of drug development. Topics covered include an overview of antibody development, PK characteristics, and the application of antibody PK/pharmacodynamics (PD) in research and development decision-making. We also discuss the general considerations for planning a nonclinical PK program and describe the types of PK studies that should be performed during early development of monoclonal antibodies.
Topics: Antibodies, Monoclonal; Biological Availability; Clinical Trials as Topic; Decision Making; Drug Development; Half-Life; History, 21st Century; Humans; Metabolic Clearance Rate; Models, Biological; Molecular Targeted Therapy; Tissue Distribution
PubMed: 29877608
DOI: 10.1111/cts.12567 -
Skin Pharmacology and Physiology 2008
Topics: Administration, Topical; Animals; Humans; Pharmacokinetics; Skin Absorption
PubMed: 18319607
DOI: 10.1159/000119708