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Seminars in Arthritis and Rheumatism Dec 2023Renal safety risk is currently an important factor that hinders the development of uric acid transporter 1 (URAT1) inhibitors. This study aimed to compare the renal...
OBJECTIVE
Renal safety risk is currently an important factor that hinders the development of uric acid transporter 1 (URAT1) inhibitors. This study aimed to compare the renal safety and uric acid-lowering efficacy of different URAT1 inhibitors and clarify the association between them.
METHODS
A systematic review of published randomized controlled trials on URAT1 inhibitors was conducted to investigate the incidence of renal safety events. A model-based analysis was performed to predict the uric acid-lowering efficacy of representative URAT1 inhibitors.
RESULTS
The overall renal safety event incidences of lesinurad, verinurad, dotinurad, SHR4640, and benzbromarone in patients with hyperuricemia were 11.2 % (142/1264), 12.0 % (34/284), 0.5 % (2/421), 2.3 % (5/213), and 1.3 % (5/393), respectively. A semi-mechanistic pharmacokinetic/pharmacodynamic model was used to establish the dose-exposure-effect relationship of lesinurad, verinurad, dotinurad, and SHR4640 with or without the combination of xanthine oxidase inhibitors (XOIs). The efficacy ranking of the intermediate dose of URAT1 inhibitors with once-daily dosing was 2 mg dotinurad > 10 mg verinurad > 5 mg SHR4640 > 400 mg lesinurad. The combination of 80 mg febuxostat and 600 mg allopurinol reduced the 24-h cumulative renal uric acid excretion by 48.4 % and 48.3 %, respectively.
CONCLUSION
Uric acid-lowering efficacy is not an independent factor for the renal safety risk of different URAT1 inhibitors, and structural differences could be responsible for the difference. The adverse renal effects of URAT1 inhibitors are dose-dependent, and the combination with high doses of XOIs can significantly reduce the renal safety risk by reducing uric acid excretion by the kidneys.
PubMed: 37866004
DOI: 10.1016/j.semarthrit.2023.152279 -
Pharmacogenomics Apr 2023To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. We searched the literature up until November 2022. Preferred... (Meta-Analysis)
Meta-Analysis Review
To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. We searched the literature up until November 2022. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. 14 studies were included in qualitative analysis and seven in meta-analysis. SNVs in , , , , , , and were evaluated relative to weight loss with glucagon-like peptide-1 agonists (13 studies) or naltrexone-bupropion (one study). gene (rs1049353), gene (rs6923761, rs10305420), gene (rs7903146) were associated with weight loss in at least one study involving glucagon-like peptide-1 agonist(s). The meta-analysis did not identify any consistent effect of SNVs. Pharmacogenetic interactions for exenatide, liraglutide, naltrexone-bupropion and weight loss were identified, but the directionality was inconsistent.
Topics: Adult; Humans; Hypoglycemic Agents; Pharmacogenetics; Naltrexone; Bupropion; Peptides; Venoms; Glucagon-Like Peptide 1; Weight Loss; Glucagon-Like Peptide-1 Receptor; Diabetes Mellitus, Type 2; Protein Serine-Threonine Kinases
PubMed: 36999540
DOI: 10.2217/pgs-2022-0192 -
Pharmacogenomics Apr 2022Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but it is associated with a significant risk of severe adverse reactions... (Review)
Review
Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but it is associated with a significant risk of severe adverse reactions (ADRs) that are potentiated with the concomitant use of alcohol. Additionally, pharmacogenetic studies have explored the influence of several genetic variants in CYP450, receptors and transporters involved in the interindividual response to CLZ. Herein, we systematically review the current multiomics knowledge behind the interaction between CLZ and alcohol intake, and how its concomitant use might modulate the pharmacogenetics. and other alleles not yet discovered could support a precision medicine approach for better therapeutic effects and fewer CLZ ADRs. CLZ monitoring systems should be amended and include alcohol intake to protect patients from severe CLZ ADRs.
Topics: Alcohol Drinking; Antipsychotic Agents; Clozapine; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Schizophrenia
PubMed: 35311547
DOI: 10.2217/pgs-2022-0006 -
Paediatric Drugs Sep 2023Owing to its pharmacodynamic properties, especially the rapid onset and short duration of its action, the use of remifentanil in obstetric anesthesia, as well as in...
BACKGROUND
Owing to its pharmacodynamic properties, especially the rapid onset and short duration of its action, the use of remifentanil in obstetric anesthesia, as well as in neonatology, might be increasingly used.
OBJECTIVE
We conducted a systematic review to assess the efficacy and safety of remifentanil in preterm and term neonates. Outcomes of interest were neonatal adaptation after fetal exposure; neonatal pain, distress, and discomfort control during invasive procedures; and the occurrence of hemodynamic effects or respiratory depression induced by remifentanil infusion.
METHODS
Given the different contexts of use, we have organized this work into three parts: (A) use of remifentanil for labor or cesarean section, with exposure of the fetus before birth, (B) brief use for neonatal procedural analgesia, and (C) prolonged use for sedation/analgesia of neonates. The bibliographic search was conducted based on keywords using electronic medical databases (DATABASE, Cochrane Library, PubMed, and EMBASE) from 1 January 2000 until 31 December 2022.
RESULTS
Twenty-two articles were included (10 in part A, 5 in part B and 7 in part C). Prospective, controlled, randomized, blinded, and intention-to-treat trials were retained. Neonates were well adapted after exposure to remifentanil in the fetal period. Pain, stress, and discomfort were controlled during a brief or prolonged invasive procedure when remifentanil was used for sedation/analgesia. The physiological parameters were stable and the procedures were straightforward. Chest wall rigidity appeared to be a common side effect, but this can be managed by slow and continuous infusion and by using the minimum effective dose.
CONCLUSIONS
Remifentanil appears to be effective and safe in the short term in preterm and full-term neonates. However, its safety is compromised by the risk of chest wall rigidity. It should be used in appropriate neonatal units and in the presence of physicians able to monitor its side effects. Long-term outcomes have not been evaluated, to our knowledge.
Topics: Infant, Newborn; Humans; Pregnancy; Female; Remifentanil; Piperidines; Analgesics, Opioid; Cesarean Section; Prospective Studies; Fetus; Pain
PubMed: 37541994
DOI: 10.1007/s40272-023-00583-w -
Frontiers in Pharmacology 2023Ciprofol (HSK3486) is a novel intravenous anesthetic agent that bears structural similarity to propofol and displays favorable pharmacodynamic characteristics such as...
Ciprofol (HSK3486) is a novel intravenous anesthetic agent that bears structural similarity to propofol and displays favorable pharmacodynamic characteristics such as rapid onset and offset. The meta-analysis aimed at comparing the efficacy and safety of ciprofol versus propofol in clinical practice. Medline, EMBASE, Google Scholar, Cochrane Library were searched from inception to April 2023. The primary outcome was success rate of sedation/anesthetic induction and differences in sedation/induction time. The secondary outcomes included risks of hemodynamic instability, respiratory complications, and pain on injection, as well as recovery profiles, satisfaction score, and top-up dose requirement. Twelve RCTs (sedation: = 6, anesthetic induction, = 6, all conducted in China) involving 1,793 patients (age: 34-58 years) published from 2021 to 2023 were analyzed. Pooled results revealed no differences in success rate [risk ratio (RR) = 1, 95% confidence interval (CI): 0.99 to 1.01, I = 0%, 1,106 patients, = 1] and time required for successful anesthetic induction/sedation [mean difference (MD) = 7.95 s, 95% CI: -1.09 to 16.99, I = 97%, 1,594 patients, = 0.08]. The risks of top-up dose requirement (RR = 0.94, = 0.48), cardiopulmonary complications [i.e., bradycardia (RR = 0.94, = 0.67), tachycardia (RR = 0.83, = 0.68), hypertension (RR = 1.28, = 0.2), hypoxemia/pulmonary depression (RR = 0.78, = 0.24)], and postoperative nausea/vomiting (RR = 0.85, = 0.72), as well as discharge time (MD = 1.39 min, = 0.14) and satisfaction score (standardized MD = 0.23, = 0.16) did not differ significantly between the two groups. However, the ciprofol group had lower risks of hypotension (RR = 0.85, = 0.02) and pain on injection (RR = 0.17, < 0.00001) than the propofol group. The time to full alertness was statistically shorter in the propofol group (i.e., 0.66 min), but without clinical significance. Our results demonstrated similar efficacy between ciprofol and propofol for sedation and anesthetic induction, while ciprofol was associated with lower risks of hypotension and pain on injection. Future studies are warranted to evaluate the efficacy and safety of ciprofol in pediatric or the elderly populations. (https://www.crd.york.ac.uk/prospero/), identifier (CRD42023421278).
PubMed: 37818194
DOI: 10.3389/fphar.2023.1225288 -
Journal of Ethnopharmacology Jan 2024Epimedium koreanum Nakai (E. koreanum), a member of the genus Epimedium in the family Berberidaceae, is a well-known and well-liked traditional herb used as a "kidney... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Epimedium koreanum Nakai (E. koreanum), a member of the genus Epimedium in the family Berberidaceae, is a well-known and well-liked traditional herb used as a "kidney tonic". For thousands of years, it has been utilized for renal yang deficiency, impotence, spermatorrhea, impotence, weakness of tendons and bones, rheumatic paralysis and discomfort, numbness, and constriction.
AIM OF THE STUDY
The paper aims to comprehensively in-depth, and methodically review the most recent research on the traditional uses, phytochemistry, pharmacology, and toxicity of E. koreanum.
MATERIALS AND METHODS
Scientific databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, Baidu Scholar, and CNKI and medicine books in China were searched for relevant information on E. koreanum.
RESULTS
In traditional uses, E. koreanum is frequently used to treat various diseases like erectile dysfunction, infertility, rheumatoid arthritis, osteoporosis, asthma, kidney-yang deficiency syndrome, etc. To date, more than 379 compounds have been discovered from various parts of E. koreanum, including flavonoids, lignans, organic acids, terpenoids, hydrocarbons, dihydrophenanthrene derivatives, alkaloids, and others. Research has revealed that the compounds and crude extracts have a wide range of pharmacological effects on the reproductive, cardiovascular, and nervous systems, as well as anti-osteoporosis, anti-tumor, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, and antiviral properties. Besides, the crude extracts show potential hepatotoxicity.
CONCLUSION
Based on recent domestic and international research investigations, E. koreanum contains a wealth of chemical components with pronounced pharmacological activities. Its traditional uses are numerous, and the majority of these traditional uses have been supported by contemporary pharmacological investigations. Crude extracts, on the other hand, can result in hepatotoxicity. Therefore, additional in vivo and in vitro experimental research on the pharmacology and toxicology of E. koreanum are required in the future to assess its safety and efficacy. This will give a firmer scientific foundation for its safe application and the development of new drugs in the future.
Topics: Male; Humans; Phytotherapy; Epimedium; Yang Deficiency; Erectile Dysfunction; Chemical and Drug Induced Liver Injury; Phytochemicals; Ethnopharmacology; Plant Extracts; Medicine, Chinese Traditional
PubMed: 37544344
DOI: 10.1016/j.jep.2023.116957 -
Clinical and Translational Science Dec 2023Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals'... (Review)
Review
Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals' (HCPs) and consumers' knowledge, attitudes, perspectives, and education needs to inform strategies for implementation of scalable and sustainable oncology PGx programs. Systematic review of original articles indexed in EMBASE, EMCARE, MEDLINE, and PsycInfo from January 2012 until June 2022, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using the Mixed Methods Appraisal Tool. PROSPERO registration number CRD42022352348. Of 1442 identified studies; 23 met inclusion criteria with 87% assessed high quality. Of these, 52% reported on HCPs, 35% on consumers, and 13% on both HCPs and consumers. Most were conducted in the United States (70%) and included multiple cancer types (74%). Across studies, HCPs and consumers mostly perceived value in PGx, however, both groups reported barriers to utilization, including cost, lack of consistent recommendations across guidelines, and limited knowledge among HCPs; test accuracy, clear testing benefits, and genomic information confidentiality among consumers. HCPs and consumers value and want to engage in PGx strategies in oncology care, however, are inhibited by unmet needs and practice and knowledge gaps. Implementation strategies aimed at addressing these issues may best support increased PGx uptake in oncology practice.
Topics: Humans; Pharmacogenetics; Health Knowledge, Attitudes, Practice; Health Personnel; Medical Oncology; Neoplasms
PubMed: 37991131
DOI: 10.1111/cts.13672 -
Clinical Toxicology (Philadelphia, Pa.) Nov 2022Silymarin is an herbal remedy, commonly called milk thistle, or St. Mary's Thistle, and has been used for over 2000 years. It has been available as a capsule of the...
Silymarin is an herbal remedy, commonly called milk thistle, or St. Mary's Thistle, and has been used for over 2000 years. It has been available as a capsule of the plant extract in Europe since 1974 to treat hepatic disorders. To date toxicologists have relied on animal studies, human case series, or retrospective reviews to decide on its use. In the U.S. the ability to use IV silibinin, its pharmacologically active purified flavonolignan, is hindered by its lack of availability as a Food and Drug Administration approved pharmaceutical preparation. This commentary reviews the studies, animal studies, and human retrospective analyses which form the basis for its clinical use. Despite the numerous publications, summarized in this issue in a systematic review, the mortality rate from Amanita mushroom ingestion remains stubbornly the same over four decades of use, and hovers around 10%. Although in the retrospective systematic review the use of silibinin, or penicillin, compared to routine care is statistically significantly superior when the primary outcome is fatality. Despite this there is no quality randomized trial to definitively demonstrate its utility. While, intravenous silibinin has a low toxicity, unanswered is whether it is useful in protecting the liver in cases of amanitin-containing mushrooms toxicity, and whether earlier administration would likely improve outcomes.
Topics: United States; Animals; Humans; Silybin; Mushroom Poisoning; Herbal Medicine; Retrospective Studies; Plant Extracts; Plants, Medicinal
PubMed: 36222816
DOI: 10.1080/15563650.2022.2128815 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Dec 2023Since the emergence of the term "materia medica", scholars have proposed different opinions on its concept. This term has been used to refer to traditional...
Since the emergence of the term "materia medica", scholars have proposed different opinions on its concept. This term has been used to refer to traditional Chinese medicines, or medical books, or traditional pharmacology. Due to the differences in the concept of materia medica, scholars also have controversies about the concept of herbalism. Herbalism is usually understood as traditional Chinese pharmacology. After years of evolution, the term "herbalism" has now possessed the characteristics of an independent discipline, which can be defined as an applied basic discipline that comprehensively utilizes traditional and modern technological methods to study the formation, development, and changes of traditional pharmacology and reveal the basic theories and application laws of traditional medicine. At present, the research content of herbalism mainly includes three aspects: materia medica history, materia medica literature, and traditional pharmacology. This study explores the disciplinary concepts and main research content of herbalism based on a systematic review of the literature about the concepts of materia medica and herbalism, with the aim of attracting more attention to promote the establishment and development of the discipline of herbalism.
Topics: China; Drugs, Chinese Herbal; Herbal Medicine; Materia Medica; Medicine, Chinese Traditional; Technology
PubMed: 38212009
DOI: 10.19540/j.cnki.cjcmm.20230927.101 -
Expert Review of Clinical Pharmacology 2023Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have... (Review)
Review
INTRODUCTION
Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have been performed to identify factors contributing to the variability and thus facilitate individualized dosing. This review aims to provide a comprehensive overview of published population pharmacokinetic studies and explore potential covariates.
METHODS
We systematically searched PubMed, Web of Science, and EMBASE databases from their inception to 31 December 2022. Information on the study design, characteristics, and final parameter estimates was summarized and compared. Monte Carlo simulations provided visual predictive distributions to compare eligible studies. Forest plots were constructed to explore the effects of covariates on olanzapine pharmacokinetics.
RESULTS
A total of 10 population pharmacokinetic and three population pharmacokinetic/pharmacodynamic studies involving infants, children, adolescents, and adults were finally included. The median apparent clearance was 0.253 L/h/kg in adults, 27-43% lower than that of infants and children. Men and smokers increased the apparent clearance of olanzapine by 32% and 34%, respectively. The concentration required to achieve half of the maximum effect for the Positive and Negative Syndrome Scale total score was 24.80 ng/mL, comparable with 22.32 ng/mL for dopamine D receptor occupancy.
CONCLUSIONS
A higher dosage may be required for men or heavy smokers than for women or nonsmokers to reach the same exposure. Moreover, further population studies are essential to be conducted to clarify the dose-exposure-response relationship of olanzapine.
PROSPERO REGISTRATION
CRD42022368637.
Topics: Male; Adult; Child; Infant; Adolescent; Humans; Female; Olanzapine; Antipsychotic Agents; Schizophrenia; Research Design; Models, Biological
PubMed: 37231707
DOI: 10.1080/17512433.2023.2219055