Pharmacology Research & Perspectives最新文献_第10页

Integrase inhibitor drugs during pregnancy and congenital anomalies: A case/non-case study from the global pharmacovigilance database VigiBase®. 孕期服用整合酶抑制剂药物与先天性畸形：来自全球药物警戒数据库 VigiBase® 的病例/非病例研究。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1247

Laura Saint-Lary, Isabelle Lacroix, Valériane Leroy, Agnès Sommet

{"title":"Integrase inhibitor drugs during pregnancy and congenital anomalies: A case/non-case study from the global pharmacovigilance database VigiBase®.","authors":"Laura Saint-Lary, Isabelle Lacroix, Valériane Leroy, Agnès Sommet","doi":"10.1002/prp2.1247","DOIUrl":"10.1002/prp2.1247","url":null,"abstract":"In 2018, a significant neural tube defects (NTD) signal was reported after pre-conceptional exposure to dolutegravir, but was not confirmed in further analysis. Since 2019, dolutegravir-based regimen, an integrase inhibitor (INI), is recommended by WHO as the most-effective first-line therapy in all patients living with HIV. To explore the potential INI-related teratogenic effect, we searched disproportionate signals between exposure to INI-class drugs and congenital anomalies, compared to non-INI drugs, using the international pharmacovigilance database, VigiBase®. We selected all the reports registered in VigiBase® between 01/01/2007 and 30/03/2021 on any antiretroviral drug-related fetal or neonatal adverse drug reactions, declared either in children (<2 years) exposed in utero or in pregnant women (12-50 years). A case/non-case study was conducted to detected signals between congenital anomalies and prenatal exposure to any INI-class drug, compared to non-INI drugs, by estimating adjusted reporting odds ratios (aROR) with 95% confidence intervals (95%CI). We identified 2521 unique reports, among which 664 (26.3%) were related to INI-class use. Overall, 520 congenital anomalies were cited from 327 unique reports, of whom 31.0% were INI-related. Compared to non-INI drugs, no significant disproportionate reporting signal between prenatal exposure to INI-class drugs and congenital anomalies was found (aROR 1.13; 95% CI:0.85-1.51). However, specific significant signals were reported for raltegravir/elvitegravir/dolutegravir drug exposure and urinary malformations (aROR 2.43; 95%CI:1.08-5.43), digestive malformations (aROR 3.09; 95%CI:1.22-7.84), and NTDs (aROR 3.02; 95%CI:1.09-8.37). Although specific congenital anomalies signals associated with raltegravir/elvitegravir/dolutegravir exposure were notified, causal relationship needs to be further investigated in prospective studies.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1247"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

No dose adjustment of metformin or substrates of organic cation transporters (OCT)1 and OCT2 and multidrug and toxin extrusion protein (MATE)1/2K with fostemsavir coadministration based on modeling approaches. 根据建模方法，二甲双胍或有机阳离子转运体（OCT）1和OCT2以及多药和毒素挤出蛋白（MATE）1/2K与福斯替沙韦联合用药时无需调整剂量。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1238

Dung Nguyen, Xiusheng Miao, Kunal Taskar, Mindy Magee, Pete Gorycki, Katy Moore, Guoying Tai

{"title":"No dose adjustment of metformin or substrates of organic cation transporters (OCT)1 and OCT2 and multidrug and toxin extrusion protein (MATE)1/2K with fostemsavir coadministration based on modeling approaches.","authors":"Dung Nguyen, Xiusheng Miao, Kunal Taskar, Mindy Magee, Pete Gorycki, Katy Moore, Guoying Tai","doi":"10.1002/prp2.1238","DOIUrl":"10.1002/prp2.1238","url":null,"abstract":"Fostemsavir is an approved gp120-directed attachment inhibitor and prodrug for the treatment of human immunodeficiency virus type 1 infection in combination with other antiretrovirals (ARVs) in heavily treatment-experienced adults with multi-drug resistance, intolerance, or safety concerns with their current ARV regimen. Initial in vitro studies indicated that temsavir, the active moiety of fostemsavir, and its metabolites, inhibited organic cation transporter (OCT)1, OCT2, and multidrug and toxin extrusion transporters (MATEs) at tested concentration of 100 uM, although risk assessment based on the current Food and Drug Administration in vitro drug-drug interaction (DDI) guidance using the mechanistic static model did not reveal any clinically relevant inhibition on OCTs and MATEs. However, a DDI risk was flagged with EMA static model predictions. Hence, a physiologically based pharmacokinetic (PBPK) model of fostemsavir/temsavir was developed to further assess the DDI risk potential of OCT and MATEs inhibition by temsavir and predict changes in metformin (a sensitive OCT and MATEs substrate) exposure. No clinically relevant impact on metformin concentrations across a wide range of temsavir concentrations was predicted; therefore, no dose adjustment is recommended for metformin when co-administered with fostemsavir.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1238"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An open-label study to explore the optimal design of CYP3A drug-drug interaction clinical trials in healthy Chinese people. 一项开放标签研究，探索在健康中国人中进行 CYP3A 药物相互作用临床试验的最佳设计。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1252

Jingcheng Chen, Jiangshuo Li, Jingxuan Wu, Yuqin Song, Lijun Li, Jianxiong Zhang, Ruihua Dong

{"title":"An open-label study to explore the optimal design of CYP3A drug-drug interaction clinical trials in healthy Chinese people.","authors":"Jingcheng Chen, Jiangshuo Li, Jingxuan Wu, Yuqin Song, Lijun Li, Jianxiong Zhang, Ruihua Dong","doi":"10.1002/prp2.1252","DOIUrl":"10.1002/prp2.1252","url":null,"abstract":"A drug-drug interaction (DDI) trial of cytochrome P450 3A (CYP3A) is a necessary part of early-phase trials of drugs mainly metabolized by this enzyme, but CYP3A DDI clinical trials do not have a standard design, especially for Chinese people. We aimed to offer specific recommendations for CYP3A DDI clinical trial design. This was an open, three-cycle, self-controlled study. Healthy subjects were given different administration strategies of CYP3A4 perpetrators. In each cycle, blood samples were collected before and within 24 h after the administration of midazolam, the CYP3A indicator substrate. The plasma concentrations of midazolam and 1-hydroxymidazolam was obtained using liquid chromatography tandem mass spectrometry assay. For CYP3A inhibition, itraconazole exposure with a loading dose could increase the exposure of midazolam by 3.21-fold based on maximum plasma concentration (Cmax), 8.37-fold based on area under the curve Pharmacology Research & Perspectives for review only from zero to the time point (AUC0-t), and 11.22-fold based on area under the curve from zero to infinity (AUC0-∞). The data were similar for itraconazole pretreatment without a loading dose. For CYP3A induction, the exposure of rifampin for 7 days decreased the plasma concentration of midazolam ~0.27-fold based on Cmax, ~0.18-fold based on AUC0-t, and ~0.18-fold based on AUC0-∞. Midazolam exposure did not significantly change when the pretreatment of rifampin increased to 14 days. This study showed that itraconazole pretreatment for 3 days without a loading dose was enough for CYP3A inhibition, and pretreatment with rifampin for 7 days could induce near-maximal CYP3A levels.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1252"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of intra- and inter-individual variations in plasma belimumab concentrations in adult patients with systemic lupus erythematosus. 评估系统性红斑狼疮成年患者血浆中贝利木单抗浓度的个体内和个体间差异。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1255

Chisato Yoshijima, Yosuke Suzuki, Ryota Tanaka, Hiroyuki Ono, Ayako Oda, Takashi Ozaki, Hirotaka Shibata, Hiroki Itoh, Keiko Ohno

{"title":"Evaluation of intra- and inter-individual variations in plasma belimumab concentrations in adult patients with systemic lupus erythematosus.","authors":"Chisato Yoshijima, Yosuke Suzuki, Ryota Tanaka, Hiroyuki Ono, Ayako Oda, Takashi Ozaki, Hirotaka Shibata, Hiroki Itoh, Keiko Ohno","doi":"10.1002/prp2.1255","DOIUrl":"10.1002/prp2.1255","url":null,"abstract":"In this study, plasma belimumab concentrations were measured over the course of treatment in systemic lupus erythematosus (SLE) patients on belimumab therapy, and intra- and interindividual variations in plasma belimumab concentration were evaluated. A single-center prospective study was conducted at Oita University Hospital to evaluate trough plasma concentrations over the course of treatment in 13 SLE patients treated with intravenous belimumab. Plasma belimumab concentrations were measured by a validated ultra-high performance liquid chromatography with tandem mass spectrometry method. The median age of the patients was 40 (interquartile range: 35-51) years and the median weight was 51.8 (47.0-58.1) kg. A mean of 9.4 (range: 1-13) blood samples was collected per patient at routine visits. The mean (± SD) plasma belimumab concentration was 33.4 ± 11.9 μg/mL in the patient with the lowest concentration and 170.0 ± 16.6 μg/mL in the patient with the highest concentration, indicating a 5-fold difference between patients. On the other hand, the within-patient coefficient of variation ranged from 7.1% to 35.7%, showing no large variations. No significant correlation was observed between plasma belimumab concentration and belimumab dose (mg/kg) (Spearman's rank correlation coefficient = 0.22, p = .54). Examinations of trough plasma belimumab concentrations over the course of treatment in patients with SLE showed small intraindividual variation but large interindividual variation. Plasma belimumab trough concentration varied widely among patients administered the approved dose.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1255"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function. 对轻度或中度肝功能损害或肝功能正常的参与者进行索替列司他药代动力学和安全性的 1 期研究。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1213

Wei Yin, Pranab Mitra, Veronique Copalu, Thomas C Marbury, Juan Carlos Rondon, Eric J Lawitz, Valerie Lloyd, Mike Baratta, Mahnaz Asgharnejad, Tom Hui, Yasir Khan

{"title":"Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function.","authors":"Wei Yin, Pranab Mitra, Veronique Copalu, Thomas C Marbury, Juan Carlos Rondon, Eric J Lawitz, Valerie Lloyd, Mike Baratta, Mahnaz Asgharnejad, Tom Hui, Yasir Khan","doi":"10.1002/prp2.1213","DOIUrl":"10.1002/prp2.1213","url":null,"abstract":"This phase 1, open-label, three-arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK-935) in participants with hepatic impairment. Participants aged ≥18 to <75 years had moderate (Child-Pugh B) or mild (Child-Pugh A) hepatic impairment or normal hepatic function (matched to hepatic-impaired participants by sex, age, and body mass index). Soticlestat was administered as a single oral 300 mg dose. Pharmacokinetic parameters of soticlestat and its metabolites TAK-935-G (M3) and M-I were assessed and compared by group. The incidence of treatment-emergent adverse events (TEAEs) and other safety parameters were also monitored. The pharmacokinetic analyses comprised 35 participants. Participants with moderate hepatic impairment had lower proportions of bound and higher proportions of unbound soticlestat than participants with mild hepatic impairment and normal hepatic function. Total plasma soticlestat pharmacokinetic parameters (maximum observed concentration [Cmax], area under the concentration-time curve from time 0 to time of last quantifiable concentration [AUClast], and AUC from time 0 to infinity [AUC∞]) were approximately 115%, 216%, and 199% higher with moderate and approximately 45%, 35%, and 30% higher with mild hepatic impairment, respectively, than healthy matched participants. Moderate hepatic impairment decreased the liver's ability to metabolize soticlestat to M-I; glucuronidation to M3 was also affected. Mild hepatic impairment resulted in a lower total plasma M-I exposure, but glucuronidation was unaffected. TEAEs were similar across study arms, mild, and no new safety findings were observed. A soticlestat dose reduction is required for individuals with moderate but not mild hepatic impairment.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1213"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioequivalence study of low dose drospirenone/ethinyl estradiol 3 mg/0.03 mg film tablets under fasting conditions in Turkish healthy female subjects. 空腹条件下土耳其健康女性受试者服用低剂量屈螺酮/炔雌醇 3 毫克/0.03 毫克薄膜片剂的生物等效性研究。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1253

Ahmet Inal, Zafer Sezer, Berna Uluözlü, Melih Oflas, Martin Reinsch, Wolfgang Martin, Mümtaz M Mazicioglu, Selma Alime Koru

{"title":"Bioequivalence study of low dose drospirenone/ethinyl estradiol 3 mg/0.03 mg film tablets under fasting conditions in Turkish healthy female subjects.","authors":"Ahmet Inal, Zafer Sezer, Berna Uluözlü, Melih Oflas, Martin Reinsch, Wolfgang Martin, Mümtaz M Mazicioglu, Selma Alime Koru","doi":"10.1002/prp2.1253","DOIUrl":"10.1002/prp2.1253","url":null,"abstract":"This bioequivalence research aims to evaluate the relative bioavailability and pharmacokinetic characteristics of ethinyl estradiol and drospirenone in the test preparation in comparison to the reference preparation during fasting conditions. A liquid chromatography method with tandem mass spectrometry was used to determine the concentrations of drospirenone and ethinyl estradiol in plasma. The pharmacokinetic parameters that were analyzed were the maximum plasma concentration (Cmax), time to achieve Cmax (tmax), elimination half life, and area under the concentration time curve of plasma (AUC0-t, AUC0-∞ for ethinyl estradiol, and AUC0-72h for drospirenone). Both the AUC and Cmax parameters were determined to be between 80.00% and 125.00% (90% confidence intervals), which is the acceptable range. Based on the study findings, it was concluded that the test formulation, which includes 3 mg of drospirenone and 0.03 mg of ethinyl estradiol, demonstrated bioequivalence when compared to the reference formulation.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1253"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miRNA and leptin signaling in metabolic diseases and at extreme environments. 代谢性疾病和极端环境中的 miRNA 和瘦素信号转导。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1248

Samrita Mondal, Richa Rathor, Som Nath Singh, Geetha Suryakumar

{"title":"miRNA and leptin signaling in metabolic diseases and at extreme environments.","authors":"Samrita Mondal, Richa Rathor, Som Nath Singh, Geetha Suryakumar","doi":"10.1002/prp2.1248","DOIUrl":"10.1002/prp2.1248","url":null,"abstract":"The burden of growing concern about the dysregulation of metabolic processes arises due to complex interplay between environment and nutrition that has great impact on genetics and epigenetics of an individual. Thereby, any abnormality at the level of food intake regulating hormones may contribute to the development of metabolic diseases in any age group due to malnutrition, overweight, changing lifestyle, and exposure to extreme environments such as heat stress (HS), cold stress, or high altitude (HA). Hormones such as leptin, adiponectin, ghrelin, and cholecystokinin regulate appetite and satiety to maintain energy homeostasis. Leptin, an adipokine and a pleiotropic hormone, play major role in regulating the food intake, energy gain and energy expenditure. Using in silico approach, we have identified the major genes (LEP, LEPR, JAK2, STAT3, NPY, POMC, IRS1, SOCS3) that play crucial role in leptin signaling pathway. Further, eight miRNAs (hsa-miR-204-5p, hsa-miR-211-5p, hsa-miR-30, hsa-miR-3163, hsa-miR-33a-3p, hsa-miR-548, hsa-miR-561-3p, hsa-miR-7856-5p) from TargetScan 8.0 database were screened out that commonly target these genes. The role of these miRNAs should be explored as they might play vital role in regulating the appetite, energy metabolism, metabolic diseases (obesity, type 2 diabetes, cardiovascular diseases, inflammation), and to combat extreme environments. The miRNAs regulating leptin signaling and appetite may be useful for developing novel therapeutics for metabolic diseases.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1248"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preclinical evaluation of ELP-004 in mice. 对 ELP-004 进行小鼠临床前评估。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1230

Jamie L McCall, Werner J Geldenhuys, Lisa J Robinson, Michelle R Witt, Peter M Gannett, Björn C G Söderberg, Harry C Blair, Jonathan Soboloff, John B Barnett

{"title":"Preclinical evaluation of ELP-004 in mice.","authors":"Jamie L McCall, Werner J Geldenhuys, Lisa J Robinson, Michelle R Witt, Peter M Gannett, Björn C G Söderberg, Harry C Blair, Jonathan Soboloff, John B Barnett","doi":"10.1002/prp2.1230","DOIUrl":"10.1002/prp2.1230","url":null,"abstract":"This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP-004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease-modifying antirheumatic drugs, are not well-tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP-004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed. We found that ELP-004 was non-mutagenic, did not induce chromosome aberrations, non-cardiotoxic, and had minimal off-target effects. Using in vitro hepatic systems, we found that ELP-004 is primarily metabolized by CYP1A2 and CYP2B6 and predicted metabolic pathways were identified. Finally, we show that ELP-004 inhibits osteoclast differentiation without suppressing overall T-cell function. These preclinical data will inform future development of an oral compound as well as in vivo efficacy studies in mice.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1230"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata. 一项2a期研究，探讨利特西替尼对成人斑秃患者脑干听觉诱发电位和表皮内神经纤维组织学的影响。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1204

Samira Anderson, Guido Cavaletti, Linda J Hood, Michael Polydefkis, David N Herrmann, Gary Rance, Brett King, Amy J McMichael, Maryanne M Senna, Brian S Kim, Lynne Napatalung, Robert Wolk, Samuel H Zwillich, Gregor Schaefer, Yankun Gong, Melanie Sisson, Holly B Posner

{"title":"A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata.","authors":"Samira Anderson, Guido Cavaletti, Linda J Hood, Michael Polydefkis, David N Herrmann, Gary Rance, Brett King, Amy J McMichael, Maryanne M Senna, Brian S Kim, Lynne Napatalung, Robert Wolk, Samuel H Zwillich, Gregor Schaefer, Yankun Gong, Melanie Sisson, Holly B Posner","doi":"10.1002/prp2.1204","DOIUrl":"10.1002/prp2.1204","url":null,"abstract":"Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9-month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50-mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double-blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4-week loading dose of 200 mg QD or placebo for 9 months (placebo-controlled phase); they then entered the active-therapy extension and received ritlecitinib 50 mg QD (with a 4-week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I-V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1204"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High prevalence of medication errors in a secondary-level Lithuanian hospital: A prospective cross-sectional observational study. 立陶宛一家二级医院的用药错误高发率：前瞻性横断面观察研究。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2024-08-01 DOI: 10.1002/prp2.1246

J Butauskaite, A Zumbakyte, L Aukstikalne, J Pancere, S Zukaitiene, E Karinauske

{"title":"High prevalence of medication errors in a secondary-level Lithuanian hospital: A prospective cross-sectional observational study.","authors":"J Butauskaite, A Zumbakyte, L Aukstikalne, J Pancere, S Zukaitiene, E Karinauske","doi":"10.1002/prp2.1246","DOIUrl":"10.1002/prp2.1246","url":null,"abstract":"As the population continues to age, the occurrence of chronic illnesses and comorbidities that often necessitate the use of polypharmacy has been on the rise. Polypharmacy, among other factors that tend to coincide with chronic diseases, such as obesity, impaired kidney and liver function, and older age, can increase the risk of medication errors (MEs). Our study aims to evaluate the prevalence of MEs in the Internal medicine, Cardiology, and Neurology departments at the secondary-level university hospital. We conducted a prospective observational study of 145 patients' electronic or paper-based data of inpatient prescriptions and patients' pharmacokinetic risk factors, such as an impairment of renal and/or hepatic function, weight, and age. All included patients collectively received 1252 prescribed drugs. The median (Q1; Q3) number of drugs per patient was 8 (7;10). At least one ME was identified in 133 out of the 145 patients, indicating a significantly higher prevalence than hypothesized (91.7% vs. 50%; p < .001). There was moderate, positive correlation between the quantity of prescribed drugs and the number of MEs, meaning that the more drugs are prescribed, the higher the number of identified MEs (Spearman's ρ = 0.428; p < .001). These findings suggest that there is a need for continuous medication education activity for prescribing physicians, continuous evaluation of prescription appropriateness to objectively identify the MEs and to contribute to more rational patient treatment.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 4","pages":"e1246"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0