Drugs in Context最新文献

{"title":"Management of pre-renal transplant secondary hyperparathyroidism: parathyroidectomy versus cinacalcet.","authors":"Muhammed Ahmed Elhadedy,&nbsp;Ghada El-Kannishy,&nbsp;Ayman F Refaie,&nbsp;Hussein A Sheashaa,&nbsp;Ahmed Halawa","doi":"10.7573/dic.2022-11-5","DOIUrl":"https://doi.org/10.7573/dic.2022-11-5","url":null,"abstract":"<p><strong>Background: </strong>Secondary hyperparathyroidism is a common consequence of end-stage renal disease. Despite the efficacy of kidney transplantation in treating renal failure, many transplant recipients still suffer from persistent or tertiary hyperparathyroidism. Furthermore, the impact of secondary hyperparathyroidism therapy choices on other renal transplant outcomes is poorly understood.</p><p><strong>Methods: </strong>We retrieved the clinical data of 334 patients who received a kidney allograft between January 2007 and December 2014 at the Sheffield Teaching Hospitals, NHS Foundation Trust, United Kingdom. We identified three groups: parathyroidectomy group (34 patients), including patients who had parathyroidectomy before transplantation; cinacalcet group (31 patients), including patients who received cinacalcet before transplantation; and control group (269 patients), including patients who receive a transplant in the same period but did not have any evidence of hyperparathyroidism. We reviewed the demographic data, biochemical parameters and graft survival of all groups.</p><p><strong>Results: </strong>Patients who underwent parathyroidectomy before transplantation had significantly better post-transplant calcium and parathyroid hormone levels than patients in the cinacalcet group (<i>p</i>=0.003). In addition, a significantly lower number of patients had tertiary hyperparathyroidism in the parathyroidectomy group than in the cinacalcet group at 1 year of follow-up (<i>p</i>=0.001). However, short-term and long-term graft survival was comparable in all groups.</p><p><strong>Conclusions: </strong>Renal allograft survival was comparable in all groups. However, tertiary hyperparathyroidism was less likely to occur in patients who underwent parathyroidectomy than in those who were administered cinacalcet.</p>","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/be/dic-2022-11-5.PMC10108670.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9384350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-rate breakthrough cancer pain and tumour characteristics - literature review and case series.","authors":"Arturo Cuomo,&nbsp;Anastasios Boutis,&nbsp;Francesca Colonese,&nbsp;Davide Nocerino","doi":"10.7573/dic.2022-11-1","DOIUrl":"https://doi.org/10.7573/dic.2022-11-1","url":null,"abstract":"Cancer pain requires careful comprehensive patient evaluation and an appropriate and personalized clinical approach by a trained multidisciplinary team. The proper assessment of breakthrough cancer pain (BTcP) is part of an all-inclusive multidimensional evaluation of the patient. The aim of this narrative review is to explore the relationship between high-rate BTcP, which strongly impacts health- related quality of life and tumour characteristics, in the face of novel approaches that should provide guidance for future clinical practice. The presentation of short, emblematic clinical reports also promotes knowledge of BTcP, which, despite the availability of numerous therapeutic approaches, remains underdiagnosed and undertreated. This article is part of the Management of breakthrough cancer pain Special Issue: https://www.drugsincontext.com/special_issues/management-of-breakthrough-cancer-pain","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/e5/dic-2022-11-1.PMC10012833.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9131125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necessity of vancomycin trough concentrations to manage uncomplicated acute bacterial skin and skin structure infections: a laboratory stewardship analysis.","authors":"Andrew Merker,&nbsp;Kartik Anne,&nbsp;Justin Rayyan,&nbsp;Milena Murray","doi":"10.7573/dic.2023-2-1","DOIUrl":"https://doi.org/10.7573/dic.2023-2-1","url":null,"abstract":"<p><strong>Background: </strong>Recent recommendations by the American Society of Health System Pharmacists and Infectious Disease Society of America have provided guidance regarding vancomycin dosing and monitoring in serious infections (including methicillin-resistant <i>Staphylococcus aureus</i>); however, trough monitoring for uncomplicated acute bacterial skin and skin structure infections (ABSSSI) were not addressed. Vancomycin use appears to lead to a low incidence of acute kidney injury with short durations and a low trough goal (10-15 mg/L). Nevertheless, clinical studies have found no difference in clinical outcomes for ABSSSI regardless of vancomycin level. Therefore, it can be posed whether trough monitoring is necessary in this patient population.</p><p><strong>Methods: </strong>This is a retrospective cohort study comparing vancomycin therapy duration for ABSSSI in adult, general medicine patients who received scheduled vancomycin with an initial creatinine clearance rate of ≥50 mL/minute and had at least one vancomycin trough. The objective of this study was to determine if vancomycin treatment duration differs for patients with ABSSSI with a sub-therapeutic vancomycin trough (ST; <10 mg/L) compared with therapeutic trough (TT; ≥10 mg/L).</p><p><strong>Results: </strong>There were 39 (67.2%) patients with ST compared with 19 (32.8%) with TT. A similar median vancomycin treatment duration for ST (48.25 hours) and TT (59.5 hours; <i>p</i>=0.65) was found. There was no statistical difference for hospital duration, time from last trough to vancomycin discontinuation, or incidence of acute kidney injury (<i>p</i>>0.05 for all).</p><p><strong>Conclusion: </strong>Patients with ST and TT had similar vancomycin durations and clinical outcomes. It may be prudent for institutions to address vancomycin trough laboratory stewardship and associated costs.</p>","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/70/b3/dic-2023-2-1.PMC10228332.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging concepts in heart failure management and treatment: focus on current guideline-directed medical therapy for heart failure with reduced ejection fraction.","authors":"Oscar Eduardo Ospina González,&nbsp;Diana Catalina Llanos Mejía,&nbsp;Edgardo Kaplinsky,&nbsp;Alejandro Barbagelata,&nbsp;Sergio Perrone","doi":"10.7573/dic.2022-6-4","DOIUrl":"https://doi.org/10.7573/dic.2022-6-4","url":null,"abstract":"<p><p>One of the most relevant and differentiating aspects provided by the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure is the retraction of the historical stepped and vertical pharmacological treatment scheme for heart failure with reduced ejection fraction (HFrEF). Subsequently, it was replaced by an updated algorithm that places four therapeutic families in the same initial horizontal step with an equally high degree of recommendation (class I). In this context, these four pillars, which have demonstrated a significant reduction in mortality and hospitalizations in patients with HFrEF, include (1) angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB)/angiotensin II receptor-neprilysin inhibitors (ARNi), (2) beta blockers, (3) mineralocorticoid receptor antagonists (MRA) and (4) sodium-glucose cotransporter 2 inhibitors (SGLT2is) as the main novelty. This manuscript reviews the current therapeutic algorithm with a special focus on the therapeutic value of adding an MRA (still underused in both clinical trials and real world), changing an ACEi/ARB for an ARNi and incorporating an SGLT2i in patients with HFrEF. This article is part of the <i>Emerging concepts in heart failure management and treatment</i> Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment.</p>","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/62/dic-2022-6-4.PMC9828867.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tinea pedis: an updated review.","authors":"Alexander Kc Leung,&nbsp;Benjamin Barankin,&nbsp;Joseph M Lam,&nbsp;Kin Fon Leong,&nbsp;Kam Lun Hon","doi":"10.7573/dic.2023-5-1","DOIUrl":"https://doi.org/10.7573/dic.2023-5-1","url":null,"abstract":"<p><strong>Background: </strong>Tinea pedis is one of the most common superficial fungal infections of the skin, with various clinical manifestations. This review aims to familiarize physicians with the clinical features, diagnosis and management of tinea pedis.</p><p><strong>Methods: </strong>A search was conducted in April 2023 in PubMed Clinical Queries using the key terms 'tinea pedis' OR 'athlete's foot'. The search strategy included all clinical trials, observational studies and reviews published in English within the past 10 years.</p><p><strong>Results: </strong>Tinea pedis is most often caused by <i>Trichophyton rubrum</i> and <i>Trichophyton interdigitale</i>. It is estimated that approximately 3% of the world population have tinea pedis. The prevalence is higher in adolescents and adults than in children. The peak age incidence is between 16 and 45 years of age. Tinea pedis is more common amongst males than females. Transmission amongst family members is the most common route, and transmission can also occur through indirect contact with contaminated belongings of the affected patient. Three main clinical forms of tinea pedis are recognized: interdigital, hyperkeratotic (moccasin-type) and vesiculobullous (inflammatory). The accuracy of clinical diagnosis of tinea pedis is low. A KOH wet-mount examination of skin scrapings of the active border of the lesion is recommended as a point-of-care testing. The diagnosis can be confirmed, if necessary, by fungal culture or culture-independent molecular tools of skin scrapings. Superficial or localized tinea pedis usually responds to topical antifungal therapy. Oral antifungal therapy should be reserved for severe disease, failed topical antifungal therapy, concomitant presence of onychomycosis or in immunocompromised patients.</p><p><strong>Conclusion: </strong>Topical antifungal therapy (once to twice daily for 1-6 weeks) is the mainstay of treatment for superficial or localized tinea pedis. Examples of topical antifungal agents include allylamines (e.g. terbinafine), azoles (e.g. ketoconazole), benzylamine, ciclopirox, tolnaftate and amorolfine. Oral antifungal agents used for the treatment of tinea pedis include terbinafine, itraconazole and fluconazole. Combined therapy with topical and oral antifungals may increase the cure rate. The prognosis is good with appropriate antifungal treatment. Untreated, the lesions may persist and progress.</p>","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/5b/dic-2023-5-1.PMC10321471.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9802960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"META-INSTI: metabolic adverse events following integrase strand transfer inhibitor administration in spontaneous adverse event reports.","authors":"Milena M Murray,&nbsp;Lara Fakhouri,&nbsp;Spencer E Harpe","doi":"10.7573/dic.2023-5-9","DOIUrl":"https://doi.org/10.7573/dic.2023-5-9","url":null,"abstract":"<p><strong>Background: </strong>Metabolic effects of integrase strand transfer inhibitors (INSTIs) have been reported. The FDA Adverse Event Reporting System (FAERS) is a publicly available database that captures spontaneously reported adverse events. The objective of this study was to evaluate the relationship between INSTIs and metabolic adverse events using the FAERS database.</p><p><strong>Methods: </strong>FAERS data were queried from quarter 4 of 2007 through quarter 4 of 2019 and limited to adults. The Standardized MedDRA Query for 'hyperglycaemia/new-onset diabetes mellitus' (H/DM) was used to identify metabolic adverse events of interest. Weight gain was analysed as a separate event. Reporting odds ratios (RORs) and 95% CIs were calculated for the INSTI class and individual agents.</p><p><strong>Results: </strong>Over 10.1 million FAERS reports were identified. Any INSTI was mentioned as a primary and/or secondary suspect agent in 18,400 (0.18%) reports (bictegravir: 1414 [0.01%]; dolutegravir: 7840 [0.08%]; elvitegravir: 4034 [0.04%]; raltegravir: 5551 [0.05%]). RORs (95% CI) for H/DM and weight gain for any INSTI were 1.20 (1.15-1.27) and 2.16 (1.96-2.38). For individual agents, RORs (95% CI) for H/DM and weight gain were as follows: bictegravir, 1.23 (1.10-1.37) and 6.82 (5.50-8.41); dolutegravir, 1.28 (1.19-1.39) and 1.86 (1.58-2.18); elvitegravir, 0.76 (0.56-1.02) and 1.63 (1.37-1.92); and raltegravir, 1.00 (0.90-1.11) and 3.29 (2.77-3.91). H/DM was noted in 159 bictegravir and 712 dolutegravir reports.</p><p><strong>Conclusion: </strong>Overall, H/DM was associated with bictegravir and dolutegravir and weight gain with all INSTIs. Clinicians should know the potential relationship between INSTIs and metabolic effects and institute appropriate monitoring.</p><p><strong>This paper was previously presented: </strong>META-INSTI: Metabolic Adverse Events Following Integrase Strand Transfer Inhibitor Administration in Spontaneous Adverse Event Reports. Platform Presentation. ID Week. Virtual 2020.</p>","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/dc/dic-2023-5-9.PMC10435265.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10047678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upadacitinib for the treatment of psoriatic arthritis.","authors":"Diogo Fonseca,&nbsp;Miguel Nogueira,&nbsp;Tiago Torres","doi":"10.7573/dic.2022-11-6","DOIUrl":"https://doi.org/10.7573/dic.2022-11-6","url":null,"abstract":"<p><p>Psoriatic arthritis is a chronic systemic inflammatory disease that presents with a variable clinical course and is typically associated with joint inflammation, together with cutaneous psoriasis. In recent decades, knowledge of the pathogenesis of psoriatic arthritis has advanced considerably and has allowed for development of new highly effective therapies, transforming the treatment landscape. Upadacitinib is a Janus kinase inhibitor (JAK) that is orally reversible with high selectivity for JAK1 and its signal transduction molecules. The results obtained in the phase III clinical trials (SELECT-PsA 1 and SELEC-PsA 2) demonstrated that upadacitinib was highly effective over placebo and non-inferior to adalimumab in several important domains of the disease. Improvements were observed in dactylitis, enthesitis and spondylitis as well as in physical function, pain, fatigue and overall quality of life. The safety profile of these results resembled that of adalimumab, apart from a slightly higher rate of herpes zoster infection, an increase of creatine kinase and an incidence of lymphopenia. However, none of these events was considered a serious adverse advent. Additionally, another analysis demonstrated that combining upadacitinib with methotrexate was associated with a similar efficacy to upadacitinib in monotherapy, both for patients that are naive to biologics treatment and for those previously treated with biologics. Therefore, upadacitinib is a new option for the treatment of psoriatic arthritis, presenting a series of beneficial characteristics. At this stage, it is important to collect long-term data to confirm the efficacy and safety profiles shown in clinical trials.</p>","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/92/dic-2022-11-6.PMC9983629.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10849991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deucravacitinib for the treatment of psoriatic arthritis: the evidence so far.","authors":"Ana Martins,&nbsp;Ana Maria Lé,&nbsp;Tiago Torres","doi":"10.7573/dic.2023-2-7","DOIUrl":"https://doi.org/10.7573/dic.2023-2-7","url":null,"abstract":"<p><p>Psoriatic arthritis (PsA) is a heterogeneous disease that may develop in up to 30% of patients with psoriasis. PsA mainly involves peripheral joints; however, axial skeleton and entheses can also be involved. PsA is the result of a complex interplay between an individual's genotype and environmental factors that triggers an immune response and leads to the production of a cytokine cascade. Even though there are about 17 targeted therapies for PsA, a significant percentage of patients fail to respond to such treatments, have a partial response or develop side-effects. This article aims to review the current knowledge on deucravacitinib, a new oral small molecule that selectively inhibits tyrosine kinase 2 (TYK2), for the treatment of PsA. TYK2, a member of the Janus kinase (JAK) family, is responsible for mediating intracellular signalling of cytokines involved in the pathogenesis of PsA and psoriasis, namely IL-12, IL-23, and type I interferons. Recently, deucravacitinib was approved by the FDA for the treatment of moderate-to-severe plaque psoriasis and is currently being evaluated in phase III clinical trials in PsA. In a phase II clinical trial, deucravacitinib showed sustained effectiveness in several domains of PsA, namely arthritis, enthesitis and dactylitis, was well tolerated, and had a favourable safety profile. In patients with psoriasis, deucravacitinib had shown a higher efficacy than placebo and apremilast. Deucravacitinib is a promising therapy, with a unique mechanism of action. Results from the phase III programme and studies evaluating long-term response and head-to-head comparisons with other targeted agents will be important to establishing the position of deucravacitinib in the management of PsA.</p>","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/c7/dic-2023-2-7.PMC10166261.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9507709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of silymarin in the management of deranged liver function in non-alcoholic steatohepatitis: a case report.","authors":"Yeong Yeh Lee,&nbsp;Vincent Tee","doi":"10.7573/dic.2023-2-10","DOIUrl":"https://doi.org/10.7573/dic.2023-2-10","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease is one of the main causes of elevated liver enzymes and chronic liver disease worldwide. It ranges from steatosis to steatohepatitis, leading to cirrhosis and related liver dysfunction. Silymarin is a herbal medicine, mostly used for liver disorders owing to its supposed hepatoprotective action. This report recommends silymarin in a patient with diabetes and grade II non-alcoholic steatohepatitis, confirming significant hepatoprotective effects as shown by the reduction of liver enzyme activities. This article is part of the <i>Current clinical use of silymarin in the treatment of toxic liver diseases: a case series</i> Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.</p>","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/46/dic-2023-2-10.PMC10278441.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10086643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue distribution and abuse potential of prucalopride: findings from non-clinical and clinical studies.","authors":"Katayoun Derakhchan,&nbsp;Zhen Lou,&nbsp;Hong Wang,&nbsp;Robert Baughman","doi":"10.7573/dic.2022-6-1","DOIUrl":"https://doi.org/10.7573/dic.2022-6-1","url":null,"abstract":"Background Prucalopride is a selective serotonin type 4 (5-HT4) receptor agonist indicated for treatment of chronic idiopathic constipation (CIC) in adults (2 mg orally, daily). 5-HT4 receptors are present in the central nervous system; therefore, non-clinical and clinical assessments were performed to evaluate the tissue distribution and abuse potential of prucalopride. Methods In vitro receptor-ligand binding studies were performed to assess the affinity of prucalopride (≤1 mM) for peptide receptors, ion channels, monoamine neurotransmitters and 5-HT receptors. The tissue distribution of 14C-prucalopride (5 mg base-equivalent/kg) was investigated in rats. Behavioural assessments in mice, rats and dogs after treatment with single or repeated (up to 24 months) subcutaneous or oral doses of prucalopride (0.02–640 mg/kg across species) were performed. Treatment-emergent adverse events possibly indicative of abuse potential during prucalopride CIC clinical trials were evaluated. Results Prucalopride showed no appreciable affinity for the receptors and ion channels investigated; its affinity (at ≤100 μM) for other 5-HT receptors was 150–10,000 times lower than that for the 5-HT4 receptor. In rats, <0.1% of the administered dose was found in the brain and concentrations were below the limit of detection within 24 hours. At supratherapeutic doses (≥20 mg/kg), mice and rats exhibited palpebral ptosis, and dogs exhibited salivation, eyelid tremors, decubitis, pedalling movements and sedation. All clinical treatment-emergent adverse events, possibly indicative of abuse potential, except dizziness, occurred in <1% of patients treated with prucalopride or placebo. Conclusion This series of non-clinical and clinical studies suggest low abuse potential for prucalopride.","PeriodicalId":11362,"journal":{"name":"Drugs in Context","volume":"12 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/f5/dic-2022-6-1.PMC9983627.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10838782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}