-
Lancet (London, England) Aug 2019Genomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. The idea that genetic variation can be... (Review)
Review
Genomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. The idea that genetic variation can be used to individualise drug therapy-the topic addressed here-is often viewed as within reach for genomic medicine. We have reviewed general mechanisms underlying variability in drug action, the role of genetic variation in mediating beneficial and adverse effects through variable drug concentrations (pharmacokinetics) and drug actions (pharmacodynamics), available data from clinical trials, and ongoing efforts to implement pharmacogenetics in clinical practice.
Topics: Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Pharmacogenomic Variants
PubMed: 31395440
DOI: 10.1016/S0140-6736(19)31276-0 -
Journal of Nuclear Medicine Technology Sep 2018Pharmacology principles provide a key understanding that underpins the clinical and research roles of nuclear medicine practitioners. This article is the second in a... (Review)
Review
Pharmacology principles provide a key understanding that underpins the clinical and research roles of nuclear medicine practitioners. This article is the second in a series of articles that aims to enhance the understanding of pharmacologic principles relevant to nuclear medicine. This article will build on the introductory concepts, terminology, and principles of pharmacodynamics explored in the first article in the series. Specifically, this article will focus on the basic principles associated with pharmacokinetics. Article 3 will outline pharmacology relevant to pharmaceutical interventions and adjunctive medications used in general nuclear medicine; article 4, pharmacology relevant to pharmaceutical interventions and adjunctive medications used in nuclear cardiology; article 5, pharmacology relevant to contrast media associated with CT and MRI; and article 6, drugs in the emergency cart.
Topics: Animals; Humans; Pharmaceutical Preparations; Pharmacokinetics; Pharmacology
PubMed: 29724803
DOI: 10.2967/jnmt.117.199638 -
Journal of Nuclear Medicine Technology Jun 2018There is an emerging need for greater understanding of pharmacology principles among technical staff. Indeed, the responsibility of dose preparation and administration,... (Review)
Review
There is an emerging need for greater understanding of pharmacology principles among technical staff. Indeed, the responsibility of dose preparation and administration, under any level of supervision, demands a foundational understanding of pharmacology. This is true for radiopharmaceuticals, contrast media, and pharmaceutical interventions or adjunctive medications. Regulation around the same might suggest a need to embed pharmacology theory in undergraduate education programs, and there is a need to disseminate that same foundational understanding to practicing clinicians. Moreover, pharmacology foundations can provide a key understanding of the principles that underpin quantitative techniques (e.g., pharmacokinetics). This article is the first in a series that aims to enhance the understanding of pharmacologic principles relevant to nuclear medicine. This article will deal with the introductory concepts, terminology, and principles that underpin the concepts to be discussed in the remainder of the series. The second article will build on the pharmacodynamic principles examined in this article with a treatment of pharmacokinetics. Article 3 will outline pharmacology relevant to pharmaceutical interventions and adjunctive medications used in general nuclear medicine, article 4 will cover pharmacology relevant to pharmaceutical interventions and adjunctive medications used in nuclear cardiology, and article 5 will discuss the pharmacology related to contrast media associated with CT and MRI. The final article (6) in the series will examine the pharmacology of drugs associated with the crash cart/emergency trolley.
Topics: Animals; Drug Interactions; Humans; Pharmaceutical Preparations; Pharmacology; Receptors, Cell Surface; Terminology as Topic
PubMed: 29599397
DOI: 10.2967/jnmt.117.199588 -
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 -
Therapeutic Drug Monitoring Apr 2023Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have greatly benefitted from computational and mathematical advances over the past 60 years.... (Review)
Review
BACKGROUND
Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have greatly benefitted from computational and mathematical advances over the past 60 years. Furthermore, the use of artificial intelligence (AI) and machine learning (ML) approaches for supporting clinical research and support is increasing. However, AI and ML applications for precision dosing have been evaluated only recently. Given the capability of ML to handle multidimensional data, such as from electronic health records, opportunities for AI and ML applications to facilitate TDM and MIPD may be advantageous.
METHODS
This review summarizes relevant AI and ML approaches to support TDM and MIPD, with a specific focus on recent applications. The opportunities and challenges associated with this integration are also discussed.
RESULTS
Various AI and ML applications have been evaluated for precision dosing, including those related to concentration or exposure prediction, dose optimization, population pharmacokinetics and pharmacodynamics, quantitative systems pharmacology, and MIPD system development and support. These applications provide an opportunity for ML and pharmacometrics to operate in an integrated manner to provide clinical decision support for precision dosing.
CONCLUSIONS
Although the integration of AI with precision dosing is still in its early stages and is evolving, AI and ML have the potential to work harmoniously and synergistically with pharmacometric approaches to support TDM and MIPD. Because data are increasingly shared between institutions and clinical networks and aggregated into large databases, these applications will continue to grow. The successful implementation of these approaches will depend on cross-field collaborations among clinicians and experts in informatics, ML, pharmacometrics, clinical pharmacology, and TDM.
Topics: Humans; Artificial Intelligence; Machine Learning; Models, Biological; Precision Medicine; Pharmacology, Clinical
PubMed: 36750470
DOI: 10.1097/FTD.0000000000001078 -
Journal of Natural Products Mar 2012This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved... (Review)
Review
This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions and have added a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules, 131, or 74.8%, are other than "S" (synthetic), with 85, or 48.6%, actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the anti-infective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 30-year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly.
Topics: Biological Products; Combinatorial Chemistry Techniques; Drug Approval; History, 20th Century; History, 21st Century; Molecular Structure; Pharmacology; Research
PubMed: 22316239
DOI: 10.1021/np200906s -
Paediatric Anaesthesia Jan 2014Effective and safe drug administration in neonates should be based on integrated knowledge on the evolving physiological characteristics of the infant who will receive... (Review)
Review
Effective and safe drug administration in neonates should be based on integrated knowledge on the evolving physiological characteristics of the infant who will receive the drug and the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. Consequently, clinical pharmacology in neonates is as dynamic and diverse as the neonates we admit to our units while covariates explaining the variability are at least as relevant as median estimates. The unique setting of neonatal clinical pharmacology will be highlighted based on the hazards of simple extrapolation of maturational drug clearance when only based on 'adult' metabolism (propofol, paracetamol). Second, maturational trends are not at the same pace for all maturational processes. This will be illustrated based on the differences between hepatic and renal maturation (tramadol, morphine, midazolam). Finally, pharmacogenetics should be tailored to neonates, not just mirror adult concepts. Because of this diversity, clinical research in the field of neonatal clinical pharmacology is urgently needed and facilitated through PK/PD modeling. In addition, irrespective of already available data to guide pharmacotherapy, pharmacovigilance is needed to recognize specific side effects. Consequently, pediatric anesthesiologists should consider to contribute to improved pharmacotherapy through clinical trial design and collaboration, as well as reporting on adverse effects of specific drugs.
Topics: Body Weight; Humans; Infant, Newborn; Kidney; Liver; Pharmaceutical Preparations; Pharmacogenetics; Pharmacokinetics; Pharmacology, Clinical
PubMed: 23617305
DOI: 10.1111/pan.12176 -
The Journal of Histochemistry and... Mar 2010
Topics: Drug Discovery; Histocytochemistry; Pharmacology
PubMed: 19995944
DOI: 10.1369/jhc.2009.955534 -
Neuropsychopharmacology : Official... Jan 2012
Topics: Animals; Central Nervous System Diseases; Humans; Neuropharmacology; Psychopharmacology
PubMed: 22157854
DOI: 10.1038/npp.2011.233 -
Molecular Pharmaceutics Mar 2018
Topics: Chemistry, Pharmaceutical; Drug Discovery; Humans; Metabolic Engineering; Pharmacology; Proteomics
PubMed: 29502427
DOI: 10.1021/acs.molpharmaceut.8b00067