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Journal of Pharmaceutical Sciences Jan 2024Historically, vaccine development and dose optimization have followed mostly empirical approaches without clinical pharmacology and model-informed approaches playing a... (Review)
Review
Historically, vaccine development and dose optimization have followed mostly empirical approaches without clinical pharmacology and model-informed approaches playing a major role, in contrast to conventional drug development. This is attributed to the complex cascade of immunobiological mechanisms associated with vaccines and a lack of quantitative frameworks for extracting dose-exposure-efficacy-toxicity relationships. However, the Covid-19 pandemic highlighted the lack of sufficient immunogenicity due to suboptimal vaccine dosing regimens and the need for well-designed, model-informed clinical trials which enhance the probability of selection of optimal vaccine dosing regimens. In this perspective, we attempt to develop a quantitative clinical pharmacology-based approach that integrates vaccine dose-efficacy-toxicity across various stages of vaccine development into a unified framework that we term as model-informed vaccine dose-optimization and development (MIVD). We highlight scenarios where the adoption of MIVD approaches may have a strategic advantage compared to conventional practices for vaccines.
Topics: Humans; Pharmacology, Clinical; Pandemics; Vaccines; Drug Development; Vaccine Development; Models, Biological; Dose-Response Relationship, Drug
PubMed: 37924975
DOI: 10.1016/j.xphs.2023.10.043 -
Journal of Neurology, Neurosurgery, and... Jun 1994
Topics: France; History, 18th Century; History, 19th Century; Humans; Neurophysiology; Nutritional Physiological Phenomena; Pharmacology; Philately; South Africa
PubMed: 8006648
DOI: 10.1136/jnnp.57.6.692 -
British Journal of Clinical Pharmacology 2001Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a... (Review)
Review
Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions.
Topics: Bayes Theorem; Drug Delivery Systems; Drug Monitoring; Humans; Pharmacokinetics; Pharmacology, Clinical
PubMed: 11564053
DOI: 10.1046/j.1365-2125.2001.0520s1055.x -
Missouri Medicine 2019About half a million adverse drug reactions are reported in the US each year that result in disability, hospitalization or death. The efficacy or toxicity of a drug in a...
About half a million adverse drug reactions are reported in the US each year that result in disability, hospitalization or death. The efficacy or toxicity of a drug in a patient can be strongly influenced by their genetics as well as environment. Application of genomics to clinical pharmacology, "pharmacogenomics," promises to transform patient care and health resource utilization in the coming decade.
Topics: Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Genomics; Humans; Pharmacogenetics; Pharmacology; Physician's Role; Precision Medicine
PubMed: 31527945
DOI: No ID Found -
British Journal of Pharmacology Sep 2007This article reviews the origin and evolution of high throughput screening (HTS) through the experience of an individual pharmaceutical company, revealing some of the... (Review)
Review
This article reviews the origin and evolution of high throughput screening (HTS) through the experience of an individual pharmaceutical company, revealing some of the mysteries of the early stages of drug discovery to the wider pharmacology audience. HTS in this company (Pfizer, Groton, USA) had its origin in natural products screening in 1986, by substituting fermentation broths with dimethyl sulphoxide solutions of synthetic compounds, using 96-well plates and reduced assay volumes of 50-100 microl. A nominal 30 mM source compound concentration provided high microM assay concentrations. Starting at 800 compounds each week, the process reached a steady state of 7200 compounds per week by 1989. Screening in the Applied Biotechnology and Screening Group was centralized with screens operating in lock-step to maximize efficiency. Initial screens were full files run in triplicate. Autoradiography and image analysis were introduced for (125)I receptor ligand screens. Reverse transcriptase (RT) coupled with quantitative PCR and multiplexing addressed several targets in a single assay. By 1992 HTS produced 'hits' as starting matter for approximately 40% of the Discovery portfolio. In 1995, the HTS methodology was expanded to include ADMET targets. ADME targets required each compound to be physically detected leading to the development of automated high throughput LC-MS. In 1996, 90 compounds/week were screened in microsomal, protein binding and serum stability assays. Subsequently, the mutagenic Ames assay was adapted to a 96-well plate liquid assay and novel algorithms permitted automated image analysis of the micronucleus assay. By 1999 ADME HTS was fully integrated into the discovery cycle.
Topics: Animals; Cell Line; Cell-Free System; Databases as Topic; Diffusion of Innovation; Drug Design; Drug Evaluation, Preclinical; Drug Industry; Genetic Techniques; History, 20th Century; History, 21st Century; Humans; Ligands; Microarray Analysis; Microchemistry; Molecular Structure; Pharmacokinetics; Pharmacology; Protein Conformation; Reproducibility of Results; Structure-Activity Relationship; Toxicity Tests; United States
PubMed: 17603542
DOI: 10.1038/sj.bjp.0707373 -
Indian Journal of Pharmacology Oct 2016
Topics: Biomedical Research; Education, Medical; Humans; India; Pharmacology
PubMed: 28031597
DOI: 10.4103/0253-7613.193330 -
British Journal of Clinical Pharmacology Oct 2014Pharmacotherapy might be improved if future pharmacists and physicians receive a joint educational programme in pharmacology and pharmacotherapeutics. This study... (Comparative Study)
Comparative Study
AIM
Pharmacotherapy might be improved if future pharmacists and physicians receive a joint educational programme in pharmacology and pharmacotherapeutics. This study investigated whether there are differences in the pharmacology and pharmacotherapy knowledge and skills of pharmacy and medical students after their undergraduate training. Differences could serve as a starting point from which to develop joint interdisciplinary educational programmes for better prescribing.
METHODS
In a cross-sectional design, the knowledge and skills of advanced pharmacy and medical students were assessed, using a standardized test with three domains (basic pharmacology knowledge, clinical or applied pharmacology knowledge and pharmacotherapy skills) and eight subdomains (pharmacodynamics, pharmacokinetics, interactions and side-effects, Anatomical Therapeutic Chemical Classification groups, prescribing, prescribing for special groups, drug information, regulations and laws, prescription writing).
RESULTS
Four hundred and fifty-one medical and 151 pharmacy students were included between August 2010 and July 2012. The response rate was 81%. Pharmacy students had better knowledge of basic pharmacology than medical students (77.0% vs. 68.2% correct answers; P < 0.001, δ = 0.88), whereas medical students had better skills than pharmacy students in writing prescriptions (68.6% vs. 50.7%; P < 0.001, δ = 0.57). The two groups of students had similar knowledge of applied pharmacology (73.8% vs. 72.2%, P = 0.124, δ = 0.15).
CONCLUSIONS
Pharmacy students have better knowledge of basic pharmacology, but not of the application of pharmacology knowledge, than medical students, whereas medical students are better at writing prescriptions. Professional differences in knowledge and skills therefore might well stem from their undergraduate education. Knowledge of these differences could be harnessed to develop a joint interdisciplinary education for both students and professionals.
Topics: Adult; Clinical Competence; Cross-Sectional Studies; Drug Therapy; Female; Humans; Knowledge; Male; Middle Aged; Pharmacology; Students, Medical; Students, Pharmacy
PubMed: 24698099
DOI: 10.1111/bcp.12396 -
The AAPS Journal May 2021This article revisits 20 years of our work in developing evaluation tools adapted to non-linear mixed effect models. These hierarchical models involve a large number of... (Review)
Review
This article revisits 20 years of our work in developing evaluation tools adapted to non-linear mixed effect models. These hierarchical models involve a large number of assumptions concerning the structural evolution of the outcomes, the link between different outcomes, the variabilities in the parameters and model evaluation aims at assessing these various components, both to help guide the model building and to communicate on model adequacy for a given purpose. During our career, we have developed and extended simulation-based evaluation tools called normalised prediction discrepancies (npd) and normalised prediction distribution errors (npde), providing informative diagnostics through graphs and tests.
Topics: Computer Simulation; History, 21st Century; Models, Biological; Nonlinear Dynamics; Pharmacology
PubMed: 34009502
DOI: 10.1208/s12248-021-00597-7 -
Yakugaku Zasshi : Journal of the... 2015In this review, optimization of individualized analgesic therapy in cancer-pain patients (1), pharmacoepidemiological studies using a hospital database (DB) (2), and... (Review)
Review
In this review, optimization of individualized analgesic therapy in cancer-pain patients (1), pharmacoepidemiological studies using a hospital database (DB) (2), and other clinical and practical research studies (3) were summarized. (1) The aim of the analgesic study was to evaluate individual factors in the effects of pain-relief, and ADR of analgesics from the viewpoints of clinical pharmacokinetics and pharmacodynamics. Oxycodone, fentanyl, and gabapentin were used. For the dose escalation and ADR of oxycodone, the plasma disposition of noroxycodone regulated by CYP3A5 polymorphisms and cancer cachexia were found to be individual factors. The ADR and clinical response of fentanyl were affected by polymorphisms of CYP3A5 and ABCB1. In the pharmacokinetics of gabapentin, concomitant magnesium oxide reduced the intestinal absorption of gabapentin. (2) The aim of the DB study was to demonstrate a pharmacoepidemiological advantage using a hospital DB of a million-scale for post-marketing safety management. We tried to detect fluoroquinolone (FQ)-induced tendon disorders, because its risk ratio in Japan has not been clarified. The risk of a tendon disorder in FQ-prescribed patients was 0.082% (95%CI: 0.049-0.137%), and significantly higher than that in cephalosporin-prescribed patients. The risk ratio in FQ-prescribed patients in relation to cephalosporin-prescribed patients was 6.29 (95%CI: 2.27-17.46). (3) Individual variation of plasma exposure of free linezolid and its ratio to minimum inhibitory concentration in critically ill patients, as well as three other studies, were described. In conclusion, our achievement in accurately assessing these would contribute to medication safety and the appropriate use of medicines in clinical settings.
Topics: Humans; Neoplasms; Pain; Pain Management; Pharmacoepidemiology; Pharmacology, Clinical; Risk Factors
PubMed: 25832841
DOI: 10.1248/yakushi.14-00252 -
BMC Medical Education Nov 2022The lack of interaction and communication in pharmacology courses, especially since the onset of the coronavirus disease 2019 (COVID-19) pandemic, which required a fast...
BACKGROUND
The lack of interaction and communication in pharmacology courses, especially since the onset of the coronavirus disease 2019 (COVID-19) pandemic, which required a fast shift to remote learning at medical schools, leads to an unsatisfactory learning outcome. New interactive teaching approaches are required to improve pharmacology learning attention and interaction in remote education and traditional classrooms.
METHODS
We introduced bullet screens to pharmacology teaching. Then, a survey was distributed to first-, second- and third-year pre-clinical undergraduate medical and nursing students at the Shanghai Jiao Tong University School of Medicine from November 2020 to March 2022. We evaluated the essential features, instructional effectiveness, and entertainment value of bullet screens. Responses to structured and open-ended questions about the strengths and weaknesses of the bullet screen and overall thoughts were coded and compared between medical and nursing students.
RESULTS
In terms of essential features, bullet screens have a high degree of acceptability among students, and this novel instructional style conveniently increased classroom interaction. Considering instructional effectiveness, bullet screen may stimulate students' in-depth thinking. Meanwhile, students tended to use bullet-screen comments as a way to express their support rather than to make additional comments or to express their different viewpoints. The entertainment value of bullet screen was noteworthy. The lack of ideas might lead to relative differences between medical and nursing students, indicating that guiding the appropriate use of bullet screen is necessary.
CONCLUSIONS
The bullet screen may be popularized as an auxiliary teaching approach to promote interaction between teachers and students in the classroom as well as during remote education. It is an interesting and beneficial tool in pharmacology courses, yet there are several aspects of this device that should be improved for popularization.
Topics: Humans; China; COVID-19; Medicine; Schools, Medical; Pharmacology; Education, Medical, Undergraduate
PubMed: 36443714
DOI: 10.1186/s12909-022-03906-6