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Chemical Reviews Jan 2017
Topics: Allosteric Regulation; Drug Discovery; Pharmacology; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 28073249
DOI: 10.1021/acs.chemrev.6b00686 -
Clinical Pharmacology and Therapeutics Jul 2023
Topics: Humans; Pharmacology, Clinical; Pharmacology
PubMed: 37335056
DOI: 10.1002/cpt.2931 -
The Journal of Pharmacology and... Dec 2021
Topics: Editorial Policies; Humans; Leadership; Periodicals as Topic; Pharmacology
PubMed: 34845108
DOI: 10.1124/jpet.121.000924 -
Advances in Pharmacology (San Diego,... 2018Immunosuppressive drugs are a prerequisite in organ transplantation to prevent rejection and are also widely used in inflammatory diseases such as inflammatory bowel... (Review)
Review
Immunosuppressive drugs are a prerequisite in organ transplantation to prevent rejection and are also widely used in inflammatory diseases such as inflammatory bowel disease (IBD) or also in some hematologic malignancies-depending on the mode of action. For thiopurine analogs the polymorphic thiopurine S-methyltransferase (TPMT) was early detected to be associated with thiopurine-induced leukopenia; recent studies identified also NUDT15 to be related to this severe side effect. For drugs like methotrexate and mycophenolate mofetil a number of ADME genes like UDP-glucuronosyltransferases (UGTs) and ABC efflux transporters were investigated, however, with partly contradicting results. For calcineurin inhibitors like cyclosporine and in particular tacrolimus however, cytochrome P450 3A4 and 3A5 variants were found to significantly affect the pharmacokinetics. Genetic variants in genes encoding relevant pharmacodynamic proteins, however, lacked compelling evidence to affect the clinical outcome. This chapter reviews the current evidence on the association of pharmacogenetic traits to dose finding and clinical outcome of small-molecule immunosuppressants. Moreover this chapter critically summarizes suitability to apply pharmacogenetics in clinical practice in order to optimize immunosuppressant therapy.
Topics: Calcineurin Inhibitors; Humans; Immunosuppressive Agents; Immunotherapy; Models, Biological; Pharmacogenetics
PubMed: 29801578
DOI: 10.1016/bs.apha.2018.02.004 -
Handbook of Experimental Pharmacology 2019Pharmacology, the chemical control of physiology, emerged as an offshoot of physiology when the physiologists using chemicals to probe physiological systems became more... (Review)
Review
Pharmacology, the chemical control of physiology, emerged as an offshoot of physiology when the physiologists using chemicals to probe physiological systems became more interested in the probes than the systems. Pharmacologists were always, and in many ways still are, bound to study drugs in systems they do not fully understand. Under these circumstances, null methods were the main ways in which conclusions about biologically active molecules were made. However, as understanding of the basic mechanisms of cellular function and biochemical systems were elucidated, so too did the understanding of how drugs affected these systems. Over the past 20 years, new ideas have emerged in the field that have completely changed and revitalized it; these are described herein. It will be seen how null methods in isolated tissues gave way to, first biochemical radioligand binding studies, and then to a wide array of functional assay technologies that can measure the effects of molecules on drug targets. In addition, the introduction of molecular dynamics, the appreciation of the allosteric nature of receptors, protein X-ray crystal structures, genetic manipulations in the form of knock-out and knock-in systems and Designer Receptors Exclusively Activated by Designer Drugs have revolutionized pharmacology.
Topics: Drug Design; Humans; Pharmacology; Receptors, Cell Surface
PubMed: 31768748
DOI: 10.1007/164_2019_297 -
Biochemical Pharmacology May 2021
Topics: History, 20th Century; History, 21st Century; Humans; Laboratory Personnel; Pharmacology
PubMed: 33476573
DOI: 10.1016/j.bcp.2021.114421 -
Clinics in Laboratory Medicine Sep 2016This article introduces fundamental principles of pharmacogenetics as applied to personalized and precision medicine. Pharmacogenetics establishes relationships between... (Review)
Review
This article introduces fundamental principles of pharmacogenetics as applied to personalized and precision medicine. Pharmacogenetics establishes relationships between pharmacology and genetics by connecting phenotypes and genotypes in predicting the response of therapeutics in individual patients. We describe differences between precision and personalized medicine and relate principles of pharmacokinetics and pharmacodynamics to applications in laboratory medicine. We also review basic principles of pharmacogenetics, including its evolution, how it enables the practice of personalized therapeutics, and the role of the clinical laboratory. These fundamentals are a segue for understanding specific clinical applications of pharmacogenetics described in subsequent articles in this issue.
Topics: Genotype; Humans; Laboratories; Pharmacogenetics; Pharmacokinetics; Phenotype; Precision Medicine
PubMed: 27514461
DOI: 10.1016/j.cll.2016.05.006 -
British Journal of Clinical Pharmacology Aug 2021
Topics: Humans; Pharmacology; Pharmacology, Clinical
PubMed: 33835508
DOI: 10.1111/bcp.14789 -
Therapeutic Advances in Respiratory... 2023Drug development for idiopathic pulmonary fibrosis (IPF) has been challenging due to poorly understood disease etiology, unpredictable disease progression, highly... (Review)
Review
Drug development for idiopathic pulmonary fibrosis (IPF) has been challenging due to poorly understood disease etiology, unpredictable disease progression, highly heterogeneous patient populations, and a lack of robust pharmacodynamic biomarkers. Moreover, because lung biopsy is invasive and dangerous, making the extent of fibrosis as a direct longitudinal measurement of IPF disease progression unfeasible, most clinical trials studying IPF can only assess progression of fibrosis indirectly through surrogate measures. This review discusses current state-of-art practices, identifies knowledge gaps, and brainstorms development opportunities for preclinical to clinical translation, clinical populations, pharmacodynamic endpoints, and dose optimization strategies. This article highlights clinical pharmacology perspectives in leveraging real-world data as well as modeling and simulation, special population considerations, and patient-centric approaches for designing future studies.
Topics: Humans; Pharmacology, Clinical; Idiopathic Pulmonary Fibrosis; Biopsy; Fibrosis; Disease Progression
PubMed: 37392011
DOI: 10.1177/17534666231181537 -
The Journal of Pharmacology and... Dec 2015
Topics: Periodicals as Topic; Pharmacology; Pharmacology, Clinical
PubMed: 26511618
DOI: 10.1124/jpet.115.229138