Pharmacological Society Research Articles

Experiences from the initial 3 years of introducing the British Pharmacological Society and UK Medical Schools Council Prescribing Safety Assessment for Danish junior doctors.

The British Pharmacological Society and UK Medical Schools Council Prescription Safety Assessment (BPS/MSC PSA) is an electronic platform developed for assessing the prescription skills of medical students. Our aim was to investigate the feasibility of the BPS/MSC PSA in addressing prescribing competencies among junior doctors in a hospital setting. The Department of Clinical Pharmacology at Odense University Hospital established a Danish translated programme using the BPS/MSC PSA platform. We launched a formal 3-year programme in 2021, potentially assessing all first-year doctors at Odense University Hospital and Esbjerg Regional Hospital. Participation was followed by a survey. During the period of 2021 to 2023 n =364 doctors were invited, from which n =246 participated. The compliance rate increased from 38% in 2021 to 88% in 2023. The mean assessment score (points normalized to percentage) across n =246 participants was 71%, and 94% achieved a score of at least 50%. A subset of participants responded to the survey, with the majority of those completing the questionnaire indicating that the purpose of the assessment was clear. The items related to difficulty and number of questions received comparable evaluations, and most respondents found the questions clinically relevant. It is feasible to translate and implement the BPS/MSC PSA in a Danish hospital setting. The programme provides insight into the prescribing competencies of junior doctors and the participants are generally positive.

The affinity-efficacy problem: an essential part of pharmacology education.

A fundamental mistake in receptor theory has led to an enduring misunderstanding of how to estimate the affinity and efficacy of an agonist. These properties are inextricably linked and cannot be easily separated in any case where the binding of a ligand induces a conformation change in its receptor. Consequently, binding curves and concentration-response relationships for receptor agonists have no straightforward interpretation. This problem-the affinity-efficacy problem-remains overlooked and misunderstood despite it being recognized in 1987. To avoid the further propagation of this misunderstanding, we propose in this review that the affinity-efficacy problem should be included in the core curricula for pharmacology undergraduates proposed by the British Pharmacological Society and the International Union of Basic and Clinical Pharmacology (IUPHAR).

Maximizing insights from nonclinical safety studies in the context of rising costs and changing regulations

The traditional paradigm of non-rodent safety assessment studies, primarily reliant on non-human primates (NHPs) and dogs, is undergoing a transformation. During the 2023 Safety Pharmacology Society Annual Meeting, scientists from leading nonclinical contract organizations discussed how traditional IND-enabling studies can benefit from employing underutilized alternative non-rodent models, such as the swine. Swine offer a cost-effective approach to drug development and share many anatomical and physiological similarities with humans. The inclusion of non-traditional species in safety assessments, coupled with advanced measurement techniques, aids in de-risking compounds early on and adapting projects to the evolving cost landscape.

Innovative approaches to cardiovascular safety pharmacology assessment

This editorial prefaces the annual themed issue on safety pharmacology (SP) methods which has been published since 2004 in the Journal of Pharmacological and Toxicological Methods (JPTM). Here we highlight content derived from the 2023 Safety Pharmacology Society (SPS) meeting held in Brussels, Belgium. The meeting generated 138 abstracts, reproduced in the current volume of JPTM. As in prior years, the manuscripts reflect various areas of innovation in SP including in silico modeling of stroke volume, cardiac output and systemic vascular resistance, computational approaches that compare drug-induced proarrhythmic sensitivity of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), an evaluation of the utility of the corrected J-Tpeak and Tpeak-to-Tend parameters from the ECG as potential proarrhythmia biomarkers, and the applicability of nonclinical concentration-QTc (C-QTc) modeling of data derived from the conduct of the in vivo QTc study as a component of the core battery of safety pharmacology studies.

Development of a pharmaceutical database as an aid to the nonclinical detection of drug-induced cardiac toxicity

The Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee designed and created a publicly accessible database with an initial set of 128 pharmacologically defined pharmaceutical agents, many with known cardiotoxic properties. The database includes specific information about each compound that could be useful in evaluating hypotheses around mechanisms of drug-induced cardiac toxicity or for development of novel cardiovascular safety assays. Data on each of the compounds was obtained from published literature and online sources (e.g., DrugBank.ca and International Union of Basic and Clinical Pharmacology (IUPHAR) / British Pharmacological Society (BPS) Guide to PHARMACOLOGY) and was curated by 10 subject matter experts. The database includes information such as compound name, pharmacological mode of action, characterized cardiac mode of action, type of cardiac toxicity, known clinical cardiac toxicity profile, animal models used to evaluate the cardiotoxicity profile, routes of administration, and toxicokinetic parameters (i.e., Cmax). Data from both nonclinical and clinical studies are included for each compound. The user-friendly web interface allows for multiple approaches to search the database and is also intended to provide a means for the submission of new data/compounds from relevant users. This will ensure that the database is constantly updated and remains current. Such a data repository will not only aid the HESI working groups in defining drugs for use in any future studies, but safety scientists can also use the database as a vehicle of support for broader cardiovascular safety studies or exploring mechanisms of toxicity associated with certain pharmacological modes of action.

Canadian Society of Pharmacology and Therapeutics.

Canadian Society of Pharmacology and Therapeutics.

Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses.

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

Report on the 96th Annual Meeting of the Japanese Pharmacological Society “Pre- and Post-Survey”

Report on the 96th Annual Meeting of the Japanese Pharmacological Society “Pre- and Post-Survey”

Therapeutic targets of fibrosis: Translational advances and current challenges.

In a physiological context, the extracellular matrix (ECM) provides an important scaffold for organs. Dysregulation of ECM in disease conditions, characterised by excess deposition of connective tissue and extracellular matrix in response to a pathological insult, is a key driver of disease progression in multiple organs. The resultant fibrosis is predominantly an irreversible process and directly contributes to, and exacerbates, dysfunction of an affected organ. This is particularly paramount in the kidney, liver, heart and lung. A hybrid Joint Meeting of NC-IUPHAR and British Pharmacological Society was held in Paris and via a webinar in November 2020, when two successive sessions were devoted to translational advances in fibrosis as a therapeutic target. On the upsurge of response to these sessions, the concept of a special themed issue on this topic emerged, and is entitled Translational Advances in Fibrosis as a Therapeutic Target. In this special issue, we seek to provide an up-to-date account of the diverse molecular mechanisms and causal role that fibrosis plays in disease progression (contributing to, and exacerbating, dysfunction of affected organs). Recent developments in the understanding of molecular targets involved in fibrosis, and how their actions can be manipulated therapeutically, are included.

Embedding research into clinical care to improve health outcomes

As well as Breckenridge Chair of Clinical Pharmacology at the University of Liverpool, Professor Reecha Sofat is Vice President (Clinical) of the British Pharmacological Society and an Associate Director for the British Heart Foundation Data Science Centre. Here, Professor Sofat talks to Joy Ogden about her research to improve understanding of disease and the effective use of medicines, and how her various roles complement each other.

Polybrominated Diphenyl Ethers (PBDEs) and Human Health: Effects on Metabolism, Diabetes and Cancer.

There is increasing evidence of the role of endocrine disruptors (EDs) derived from commonly employed compounds for manufacturing and processing in altering hormonal signaling and function. Due to their prolonged half-life and persistence, EDs can usually be found not only in industrial products but also in households and in the environment, creating the premises for long-lasting exposure. Polybrominated diphenyl ethers (PBDEs) are common EDs used in industrial products such as flame retardants, and recent studies are increasingly showing that they may interfere with both metabolic and oncogenic pathways. In this article, a multidisciplinary panel of experts of the Italian Association of Medical Diabetologists (AMD), the Italian Society of Diabetology (SID), the Italian Association of Medical Oncology (AIOM), the Italian Society of Endocrinology (SIE) and the Italian Society of Pharmacology (SIF) provides a review on the potential role of PBDEs in human health and disease, exploring both molecular and clinical aspects and focusing on metabolic and oncogenic pathways.

Individualized Delivery of Vancomycin by Model-Informed Bayesian Dosing Approach to Maintain an AUC24 Target in Critically Ill Patients

Introduction: Monitoring of AUC24 was updated recommendation in the guideline for the therapeutic drug monitoring (TDM) of vancomycin in Chinese pharmacological society published in 2020. Vancomycin pharmacokinetic profiles are diverse and unique in critically ill patients because of the drastic variability of the patients’ physiological parameters, while the study for population pharmacokinetic (PPK) models in Chinese critically ill patients has been rarely reported. The objectives of this study were to construct a PPK model to describe the pharmacokinetic characteristics of vancomycin in critically ill patients and to individualize vancomycin dosing by model-informed Bayesian estimation for maintenance of AUC24 target at 400–650 mg h/L recommended by the 2020 guideline. Methods: Vancomycin with different dosing was administered intravenously over 1 h for critically ill patients, TDM was started at 48 h or 72 h since initiation of vancomycin therapy for patients. Blood samples were collected from patients for trough concentrations or Cmax. Vancomycin concentrations were determined by high-performance liquid chromatography method with ultraviolet detection. PPK model was performed using the nonlinear mixed-effect model (NONMEM®). Individual PK parameters for critically ill patients treated with vancomycin were estimated using a post hoc empirical Bayesian method based on the final PPK model. AUC24 was calculated as the total daily dose divided by the clearance (L/h). Results: The PPK of vancomycin was determined by a one-compartment model with creatinine clearance as fixed effects. The PK estimates in the final model generally agreed with the median estimates and were contained within the 95% CI generated from the bootstrap results, indicating good precision and stability in the final model. The visual predictive check plots showed the adequate predictive performance of the final PK model and supported a good model fit. The model-informed Bayesian estimation was used to predict the AUC24 of critically ill patient by the acquired TDM results, and the dosing adjustment by maintenance of AUC24 at 400–650 mg h/L had made a great therapeutic effect for the case. Conclusion: This study established a PPK model of vancomycin in Chinese critically ill patients, and individualized dosing of vancomycin by model-informed Bayesian estimation to maintain an AUC24 target at 400–650 mg h/L has been successfully applied in clinic. This result supports the continued use of model-informed Bayesian estimation to vancomycin treatment in critically ill patients.

36th Malaysian Society of Pharmacology and Physiology Annual Scientific Meeting 2023

The 36th Malaysian Society of Pharmacology and Physiology (MSPP) Annual Scientific Meeting was hosted in collaboration with the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia from the 7th to 8th of August 2023 at Bangi Resort Hotel in Bangi, Malaysia. The event focused on the theme "Pharmacology &amp; Physiology Post-Millenial Era: Challenges &amp; Opportunities". This platform is one of the suitable avenues to facilitate the exchange of scientific endeavors and enhance networking among scientists, academicians, clinicians, and postgraduate students involved in the fields of pharmacology and physiology, as well as multidisciplinary areas such as drug discovery, omics approaches, stem cells, and regenerative medicine. The primary objective of the special issue is to revitalize recent advances and breakthroughs in pharmacology and physiology to enhance opportunities and vanquish challenges in the post-millenial era, especially in the wake of the COVID-19 pandemic. In light of this, the special issue compiles the conference proceeding, to provide opportunities for knowledge integration of research and innovations.

Safety pharmacology 2023 and implementation of the ICH E14/S7B Q&A guidance document

This editorial prefaces the annual themed issue on safety pharmacology (SP) methods published since 2004 in the Journal of Pharmacological and Toxicological Methods (JPTM). We highlight here the content derived from the recent 2022 Safety Pharmacology Society (SPS) and Canadian Society of Pharmacology and Therapeutics (CSPT) joint meeting held in Montreal, Quebec, Canada. The meeting also generated 179 abstracts (reproduced in the current volume of JPTM). As in previous years the manuscripts reflect various areas of innovation in SP including a comparison of the sensitivity of cross-over and parallel study designs for QTc assessment, use of human-induced pluripotent stem cell (hi-PSC) neuronal cell preparations for use in neuropharmacological safety screening, and hiPSC derived cardiac myocytes in assessing inotropic adversity. With respect to the latter, we anticipate the emergence of a large data set of positive and negative controls that will test whether the imperative to miniaturize, humanize and create a high throughput process is offset by any loss of precision and accuracy.

Multidisciplinary expert consensus on the rational use of tetracyclines commonly used in clinical practice

In recent years, the emergence of newly detected pathogens and the increase of drug resistant bacterial bring serious challenges for the diagnosis and treatment of infectious diseases. Tetracycline drugs are widely used in clinical practice, and the varieties of these drugs are constantly being updated. However, there is still a lack of guidance documents for the rational clinical application of tetracycline drugs in China. Meanwhile, some healthcare workers have doubts about their pharmaceutical characteristics, timing and methods of clinical application. In order to further standardize the clinical application of tetracycline drugs and provide professional evidence-based medicine suggestions for medical personnel in medical institutions, under the leadership of Hospital Infection Control Branch of Chinese Preventive Medicine Association and Clinical Pharmacology Branch of Chinese Pharmacological Society, experts from areas of infection, respiratory medicine, critical care medicine, emergency, infection control, pharmacy and other disciplines organized a consensus meeting and formulated multidisciplinary expert consensus on the rational use of tetracyclines commonly used in clinical practice. This expert consensus is based on the pharmaceutical characteristics of tetracyclines commonly used in China, the mechanism of action and drug resistance status of tetracyclines, combined with the infection site, pathogen characteristics and bacterial drug resistance. This expert consensus also pays attention to special populations and off-label drug use, and integrates domestic and foreign recommendations and the latest evidence-based medicine evidence, and 17 expert consensus opinions for clinical physicians, pharmacists, and other professionals in medical institutions to refer to were formed. In view of the particularity and complexity of infectious diseases and the individual differences of patients, in order to benefit patients, individualized anti-infection strategies should be implemented.

Abstracts of the Annual Meeting of French Society of Pharmacology and Therapeutics, 12-14 June 2023, Limoges, France.

Abstracts of the Annual Meeting of French Society of Pharmacology and Therapeutics, 12-14 June 2023, Limoges, France.

Issue Information

No abstract is available for this article.

“Appraisal of state-of-the-art” The 2021 Distinguished Service Award of the Safety Pharmacology Society: Reflecting on the past to tackle challenges ahead

This appraisal of state-of-the-art manuscript highlights and expands upon the thoughts conveyed in the lecture of Dr. Jean-Pierre Valentin, recipient of the 2021 Distinguished Service Award of the Safety Pharmacology Society, given on the 2nd December 2021. The article reflects on the strengths, weaknesses, opportunities, and threats that surrounded the evolution of safety and secondary pharmacology over the last 3 decades with a particular emphasis on pharmaceutical drug development delivery, scientific and technological innovation, complexities of regulatory framework and people leadership and development. The article further built on learnings from past experiences to tackle constantly emerging issues and evolving landscape whilst being cognizant of the challenges facing these disciplines in the broader drug development and societal context.

Eleventh Triennial Toxicology Salary Survey.

This is the eleventh in a series of salary surveys for toxicologists conducted at three-year intervals that began in 1988. Previous salary surveys were conducted in 1988, 1991, 1995, 1998, 2001, 2004, 2007 (which was posted electronically, but not published), 2012, 2016 and 2020. In addition to presenting the 2022 results, herein we are providing additional data and an analysis of the trends for employment and pay in toxicology over the last 35 years. The eleventh Triennial Toxicology Salary Survey was conducted as a joint project by the American College of Toxicology (ACT) and the Society of Toxicology (SOT). In addition to the two parent organizations, eight others (the Society for Birth Defects Research, the Society of Toxicologic Pathology, the Safety Pharmacology Society, the American Board of Toxicology (ABT), the Academy of Toxicological Sciences, the Roundtable of Toxicology Consultants, the Society of Environmental Toxicology and Chemistry (SETAC), and the Environmental Mutagenesis and Genomics Society) supported the effort by distributing the Survey Monkey-based instrument to their memberships. Surveys were not distributed to regional SOT chapters, causing there to be minimal responses below the doctorate and master's degree levels. It should be noted that there continues to be a significant increase in the number of individuals reporting six-figure incomes and in those receiving significant sums as bonuses.

The prescribing safety assessment: Looking to the future.

The prescribing safety assessment: Looking to the future.