Journal of Clinical Pharmacology最新文献_第4页

From PICU to NICU: Extrapolating Meropenem Exposure From Pediatric to Neonatal Intensive Care Patients. 从PICU到NICU：从儿科到新生儿重症监护患者美罗培南暴露的推断。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-12 DOI: 10.1002/jcph.70097

Ronaldo Morales Junior, Tomoyuki Mizuno, Wen Rui Tan, Kei Irie, Sonya Tang Girdwood

{"title":"From PICU to NICU: Extrapolating Meropenem Exposure From Pediatric to Neonatal Intensive Care Patients.","authors":"Ronaldo Morales Junior, Tomoyuki Mizuno, Wen Rui Tan, Kei Irie, Sonya Tang Girdwood","doi":"10.1002/jcph.70097","DOIUrl":"10.1002/jcph.70097","url":null,"abstract":"We previously developed a population pharmacokinetic (PopPK) model for meropenem in pediatric intensive care unit patients accounting for effect of body size, maturation, and kidney function on clearance. This study aimed to extrapolate meropenem exposure to neonates and young infants using the pediatric PopPK model and to validate the predictions using external data. An independent dataset was obtained from the regulations.gov website, which included 176 neonates and young infants (up to 3 months old) with a total of 767 plasma meropenem concentrations. After normalizing the estimated glomerular filtration rate (eGFR) using a maturation factor, the PopPK model was applied to this dataset and the concordance between the model predictions and observed concentrations was visually assessed using goodness-of-fit (GOF) plots and prediction-corrected visual predictive check. Median prediction error (MDPE) evaluated bias and median absolute prediction error (MDAPE) evaluated precision of the predictions. GOF plots indicated no apparent bias or model misspecification. Individual-level predictions showed an MDPE of 1% and an MDAPE of 18.3%, both within commonly accepted thresholds for bias (<±20%-30%) and precision (<30%-35%), respectively. The findings support the model's application for simulations when neonatal eGFR is normalized using a maturation factor and for model-informed precision dosing in clinical practice for neonates and infants.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838343","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 Randomized Crossover Clinical Study to Assess the Effect of Oral Nicotine Pouches Used for Different Durations on Plasma Nicotine Pharmacokinetics in Healthy Oral Pouch Consumers. 一项随机交叉临床研究，评估不同持续时间口服尼古丁袋对健康口服尼古丁袋消费者血浆尼古丁药代动力学的影响。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-09 DOI: 10.1002/jcph.70090

David Azzopardi, Elaine Brown, Filimon Meichanetzidis, Stacy Fiebelkorn, Linsey E Haswell, George Hardie, Michael McEwan

{"title":"A Randomized Crossover Clinical Study to Assess the Effect of Oral Nicotine Pouches Used for Different Durations on Plasma Nicotine Pharmacokinetics in Healthy Oral Pouch Consumers.","authors":"David Azzopardi, Elaine Brown, Filimon Meichanetzidis, Stacy Fiebelkorn, Linsey E Haswell, George Hardie, Michael McEwan","doi":"10.1002/jcph.70090","DOIUrl":"https://doi.org/10.1002/jcph.70090","url":null,"abstract":"Oral nicotine pouches (NPs), although addictive and not risk-free, have potential application for a tobacco harm reduction approach. This study aims to further characterize their ability to deliver nicotine effectively. This randomized seven-way crossover PK study in healthy oral pouch consumers evaluated 11 and 20 mg NPs used for 10, 20, and 30 min, and for 30 min with expulsion of saliva. Used pouches were analyzed for extracted nicotine, flavor components, and sweeteners. The Cmax and AUC0-4 h increased with nicotine strength and usage time (18.9-21.6 and 26.7-33.6 ng/mL; 24.6-43.0 and 36.4 to 65.6 h ng/mL for the 11 and 20 mg NPs, respectively). Extracted nicotine was greater for the 11-mg than for the 20-mg NP, (10 min, 28.0% vs. 22.4%; 20 min, 35.8% vs. 29.6%; 30 min, 43.7% vs. 36.9%, respectively). Only 1.8% of the nicotine measured in the reference NPs was detected in saliva collected over the 30 min use period. Use of 20-mg NP for 30 min resulted in the extraction of 30.1% flavor components and 17.3% sweeteners, but only 0.16% and 3.4% of the amount measured in the reference NPs were detected in saliva, respectively. Thus, very little nicotine, flavor components, and sweeteners were swallowed during NP use. This study shows NPs can deliver nicotine effectively to satisfy smokers' nicotine desire. Nicotine delivery to the consumer increases with the duration of use. Our findings suggest that smokers who switch completely to an NP can obtain their accustomed amount of nicotine during normal product use. International Standard Registered Clinical Trial number: ISRCTN12265853.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Saliva as a TDM matrix and its application in the model-informed precision dosing. 唾液作为TDM矩阵及其在模型信息精确加药中的应用。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-06 DOI: 10.1002/jcph.70083

Baohua Xu, Yujie Wen, Jinxia Lu, Maobai Liu, Xin Luo, Wei Huang, Helin Xie, Yu Cheng, Hongqiang Qiu, Xuemei Wu

{"title":"Saliva as a TDM matrix and its application in the model-informed precision dosing.","authors":"Baohua Xu, Yujie Wen, Jinxia Lu, Maobai Liu, Xin Luo, Wei Huang, Helin Xie, Yu Cheng, Hongqiang Qiu, Xuemei Wu","doi":"10.1002/jcph.70083","DOIUrl":"https://doi.org/10.1002/jcph.70083","url":null,"abstract":"This study reviews the main points of saliva as a therapeutic drug monitoring (TDM) matrix, its advantages and limitations, the methods of saliva sample collection and testing, the types of drugs in saliva TDM, and the methods of establishing saliva population pharmacokinetic (Pop PK) models, as well as summarizes the experiences and limitations, to provide references to carry out related studies. The PubMed database was systematically searched for studies on the topic of saliva as a matrix for drug TDM. The literature was screened according to the established inclusion and exclusion criteria, and relevant data were extracted and summarized. The systematic review ultimately screened 112 articles involving relevant studies on 73 drugs, of which studies on 53 drugs supported saliva as a matrix for TDM; studies on 13 drugs did not support it; and the results of studies on seven drugs were inconsistent, with conflicting results regarding whether they supported salivary TDM or not. The study steps for Pop PK modeling based on saliva concentrations are summarized, and representative drugs for which Pop PK models incorporating both plasma and saliva concentrations have been established are listed. Saliva TDM, as a new exploration and attempt, has been confirmed to be feasible for some drugs in the current study, and is expected to be applied to the clinic in the future; Pop PK modeling based on saliva TDM for precision drug delivery has only been initially attempted for some drugs, and its application has yet to be verified in clinical studies.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disproportionality Analysis of Intravitreal Ranibizumab, Aflibercept, and Brolucizumab for Cardiovascular and Cerebrovascular Events. 玻璃体内注射雷尼单抗、阿非利塞普和布卢珠单抗治疗心脑血管事件的歧化分析。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-06 DOI: 10.1002/jcph.70094

Keisuke Nosaka, Shuji Nagano, Masaki Fujiwara, Kenta Yamaoka, Yoshihiro Uesawa, Mayako Uchida, Tadashi Shimizu

{"title":"Disproportionality Analysis of Intravitreal Ranibizumab, Aflibercept, and Brolucizumab for Cardiovascular and Cerebrovascular Events.","authors":"Keisuke Nosaka, Shuji Nagano, Masaki Fujiwara, Kenta Yamaoka, Yoshihiro Uesawa, Mayako Uchida, Tadashi Shimizu","doi":"10.1002/jcph.70094","DOIUrl":"https://doi.org/10.1002/jcph.70094","url":null,"abstract":"This study aimed to identify the potential associations between intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies (ranibizumab, aflibercept, and brolucizumab) and cardiovascular or cerebrovascular adverse events using the Japanese Adverse Drug Event Reporting (JADER) database. We conducted a disproportionality analysis using the JADER database from April 2004 to December 2024 to evaluate the cardiovascular and cerebrovascular adverse events associated with intravitreal administration of ranibizumab, aflibercept, and brolucizumab. Time-to-onset distribution and post-onset outcomes were also analyzed. Disproportional signals were observed for cerebral and myocardial infarction associated with ranibizumab and aflibercept, but not with brolucizumab. Time-to-onset analysis showed earlier onset patterns for ranibizumab than for aflibercept, with Weibull shape parameters indicating an early failure-type distribution. Post-event outcome analysis revealed some events resulting in sequelae or death, although many reports had unknown outcomes. This study identified the potential cardiovascular and cerebrovascular safety signals associated with intravitreal administration of ranibizumab and aflibercept. Although brolucizumab showed no significant disproportionality, interpretation requires caution because of limited data. Our findings underscore the importance of continued pharmacovigilance and hypothesis-driven investigations to ensure the safe use of anti-VEGF therapies.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Population Pharmacokinetics and Dosing Optimization of Piperacillin in Elderly Patients with Pneumonia in the Intensive Care Unit. 重症监护病房老年肺炎患者哌拉西林的人群药代动力学及剂量优化。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-05 DOI: 10.1002/jcph.70089

Jing Sun, Chuang Yang, Bo-Hao Tang, Guo-Xiang Hao, John van den Anker, Yue-E Wu, De-Qing Sun, Yi Zheng, Wei Zhao

{"title":"Population Pharmacokinetics and Dosing Optimization of Piperacillin in Elderly Patients with Pneumonia in the Intensive Care Unit.","authors":"Jing Sun, Chuang Yang, Bo-Hao Tang, Guo-Xiang Hao, John van den Anker, Yue-E Wu, De-Qing Sun, Yi Zheng, Wei Zhao","doi":"10.1002/jcph.70089","DOIUrl":"https://doi.org/10.1002/jcph.70089","url":null,"abstract":"Piperacillin/tazobactam is the first-line treatment for pneumonia in elderly patients. However, there are differences in dosing regimens and infusion times among different centers. We aimed to evaluate the population pharmacokinetics of piperacillin in elderly patients with pneumonia and optimize the dosing regimens. This was a prospective pharmacokinetic (PK) study of piperacillin/tazobactam in elderly patients with pneumonia using an opportunistic sampling design. The blood concentration of piperacillin was determined by high-performance liquid chromatography. A population PK model was constructed using NONMEM software, and its predictive performance was further validated in a separate test cohort. The final population PK model was used for dose optimization. A total of 151 blood samples from 73 patients were used to develop a population PK model, and 60 concentrations of therapeutic drug monitoring from 22 patients were used for model validation. A one-compartment model with first-order elimination was established. Covariate analysis showed that eGFR was the only covariate. Monte Carlo simulation results showed that for pathogens with MIC values of 8 and 16 mg/L, the dosing regimen (4000 mg every 6/8 h administered 30 min) used in this study resulted in PTAs of 23.5%-64.3%. The PTAs of the dosing regimen 4000 mg every 6 h administered by 4-h infusion for patients with different levels of renal function exceeded 90% (90.7%-99.8%), except for patients with eGFR ≥ 50 mL/min/1.73 m2.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Pharmacology Characterization and Dose Selection of Xaluritamig, a Next Generation XmAb® 2+1 T-Cell Engager, in Prostate Cancer Patients. 新一代XmAb®2+1 t细胞参与剂Xaluritamig在前列腺癌患者中的临床药理学特征和剂量选择

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-05 DOI: 10.1002/jcph.70074

Jamie N Kuipers-Connarn, Arya Pourzanjani, Maitreyee Bose, Saurabh Modi, Julia Stieglmaier, Alexis Murphy, Khamir Mehta, Vijay V Upreti

{"title":"Clinical Pharmacology Characterization and Dose Selection of Xaluritamig, a Next Generation XmAb® 2+1 T-Cell Engager, in Prostate Cancer Patients.","authors":"Jamie N Kuipers-Connarn, Arya Pourzanjani, Maitreyee Bose, Saurabh Modi, Julia Stieglmaier, Alexis Murphy, Khamir Mehta, Vijay V Upreti","doi":"10.1002/jcph.70074","DOIUrl":"https://doi.org/10.1002/jcph.70074","url":null,"abstract":"Bispecific T-cell engagers have revolutionized the treatment and management of hematological malignancies and more recently have started making similar strides for solid tumor indications, with opportunities to become best-in- class therapeutics for cancer. Xaluritamig is a novel bivalent XmAb® 2+1 T cell engager with two STEAP1 binding sites and one CD3 binding site being developed for solid tumors with the primary indication of metastatic castrate resistant prostate cancer (mCRPC). The First-In-Human (FIH) study showed promising anti-tumor activity in mCRPC patients, and the program is currently in late phase clinical development. Xaluritamig was administered as an intravenous infusion once weekly (QW) or once every other week (Q2W) in the dose escalation of the FIH study at dose levels ranging from 0.001 to 2 mg. Initial pharmacokinetic (PK) characterization of xaluritamig exhibited approximately dose-proportional increase in exposures over the dose levels explored, with an estimated terminal half-life of ≈9 days, assuming subjects had no anti-drug antibodies, calculated via the population PK model. The time at which maximum concentration (Cmax) occurred was typically at the end of infusion (median ≈ 1 h), as expected with IV administration. Additionally, thorough dose-exposure-response analyses integrated observed data and model-based simulations of PK, key efficacy endpoints, and safety events to support the evaluation of the target doses 0.75 mg QW, 1.5 mg QW, and 1.5 mg Q2W in dose expansion. This work provides the framework for which modeling and simulations can be used to guide dose selection for dose expansion at an early stage of development adhering to the recent principles of Project Optimus.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics and Bioavailability of a Novel Rivastigmine Nasal Spray Compared to Rivastigmine Oral Capsule in Healthy Men. 新型利瓦斯汀鼻喷雾剂与利瓦斯汀口服胶囊在健康男性体内的药代动力学和生物利用度比较。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-07-31 DOI: 10.1002/jcph.70086

Timothy M Morgan, Benjamin Snyder

{"title":"Pharmacokinetics and Bioavailability of a Novel Rivastigmine Nasal Spray Compared to Rivastigmine Oral Capsule in Healthy Men.","authors":"Timothy M Morgan, Benjamin Snyder","doi":"10.1002/jcph.70086","DOIUrl":"https://doi.org/10.1002/jcph.70086","url":null,"abstract":"To compare the pharmacokinetics, bioavailability, tolerability, and safety of a novel 4 mg rivastigmine nasal spray to 3 mg rivastigmine oral capsule, a single-dose, open-label, randomized, crossover study was conducted in 16 fasted healthy young men (18 to 55 years). Mean (SD) rivastigmine Cmax was 8.39 (6.8) and 13.77 (10.7) ng/mL for oral and nasal, respectively. Rivastigmine AUC0-inf was 19.6 (14.9) and 40.6 (24.4) ng h/mL for oral and nasal, respectively. The ratio of LS means (nasal test / oral reference; 90% C.I.) for rivastigmine Cmax was 185.83% (134.22, 257.28) and for rivastigmine AUC0-inf was 257.35% (197.26, 335.73). Rivastigmine tmax for nasal (0.7 h) was significantly lower than oral (1.2 h, P < .05), however, NAP226-90 tmax for nasal (1.9 h) and oral (1.8 h) were similar. NAP226-90 Cmax was 3.93 (1.1) and 3.01 (0.8) ng/mL for oral and nasal, respectively. NAP226-90 AUC0-inf was 22.9 (5.3) and 23.2 (5.1) ng h/mL for oral and nasal, respectively. Median NAP226-90 to rivastigmine AUC0-inf ratio for nasal (0.55) was significantly lower than oral (1.38, P < .05) because nasal bypassed first-pass metabolism. Both single-dose treatments were safe and well tolerated. Nasal and throat irritation were mostly perceived as mild and transient following nasal administration. The 4 mg rivastigmine nasal spray had 1.5- and 2.0-fold higher dose normalized rivastigmine Cmax and AUC0-inf, respectively, and 2.5-fold lower NAP226-90 to rivastigmine AUC0-inf ratio compared to 3 mg oral capsule. This nasal spray has good potential to improve the local and gastrointestinal tolerability of rivastigmine treatment in Alzheimer's and Parkinson's disease dementia patients.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osimertinib Cost Minimization in Non-Small Cell Lung Cancer (NSCLC) Treatment: Hypothesis Generation for a Population Pharmacokinetic Approach for Equivalent Dose Optimization of Osimertinib in Combination With Cobicistat. 奥西替尼在非小细胞肺癌（NSCLC）治疗中的成本最小化：奥西替尼与Cobicistat联合等效剂量优化的群体药代动力学方法的假设生成。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-07-31 DOI: 10.1002/jcph.70085

Niels Westra, Paul D Kruithof, Sander Croes, Robin M J M van Geel, Lizza E L Hendriks, Daan J Touw, Jos G W Kosterink, Jasper Stevens, Thijs H Oude Munnink, Paola Mian

{"title":"Osimertinib Cost Minimization in Non-Small Cell Lung Cancer (NSCLC) Treatment: Hypothesis Generation for a Population Pharmacokinetic Approach for Equivalent Dose Optimization of Osimertinib in Combination With Cobicistat.","authors":"Niels Westra, Paul D Kruithof, Sander Croes, Robin M J M van Geel, Lizza E L Hendriks, Daan J Touw, Jos G W Kosterink, Jasper Stevens, Thijs H Oude Munnink, Paola Mian","doi":"10.1002/jcph.70085","DOIUrl":"https://doi.org/10.1002/jcph.70085","url":null,"abstract":"Pharmacokinetic boosting can be a strategy to enhance osimertinib exposure and reduce treatment associated costs. The OSIBOOST trial demonstrated that it was feasible to boost low osimertinib plasma trough levels with cobicistat. The current study aims to establish the equivalent dose of cobicistat boosted osimertinib compared to osimertinib 80 mg once daily (QD) by population pharmacokinetic (popPK) modeling. A popPK model was developed on the pharmacokinetic data from the OSIBOOST study using NONMEM 7.4.4. Simulations were performed with cobicistat boosted osimertinib dosing regimens to evaluate their equivalence to the standard of osimertinib 80 mg QD. A dose level was assumed equivalent when the 90% confidence interval (CI) of the geometric mean ratios (GMR) for the area under the curve over 144 h (AUC0-144h) and maximum osimertinib concentration (Cmax) were in the acceptance range of 0.8-1.25. Cobicistat decreased osimertinib CL/F by 29.6% compared to osimertinib monotherapy (p < .0001). Osimertinib 80 mg 2 days on, 1 day off, boosted with cobicistat 150 mg QD was equivalent for osimertinib AUC0-144h (GMR [90% CI] = 0.96 [0.94-0.98]) and Cmax (GMR [90% CI] = 1.06 [1.04-1.08]) compared to osimertinib 80 mg QD monotherapy. However, this regimen was not equivalent for AZ5104 AUC0-144h (GMR [90% CI] = 0.67 [0.66-0.68]) and Cmax (GMR [90% CI] = 0.74 [0.73-0.76]). Theoretically, this reduced dose of cobicistat boosted osimertinib can potentially save approximately 33% in osimertinib treatment associated costs whilst maintaining adequate osimertinib exposure. Clinical Trials Registration: NCT03858491.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Landscape of FDA-Approved Targeted Therapies for the Treatment of Diseases with Low Frequency Molecular Subsets. fda批准的用于治疗低频分子亚群疾病的靶向疗法的概况。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-07-25 DOI: 10.1002/jcph.70081

Lois S Akinola, Sarah Ridge, Issam Zineh, Michael A Pacanowski, Anuradha Ramamoorthy

引用次数: 0

Four Pharmacogenomic Variants Strongly Linked to Corticosteroid-Induced Avascular Necrosis in Children with Cancer. 四种药物基因组变异与皮质类固醇诱导的儿童癌症缺血性坏死密切相关。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-07-25 DOI: 10.1002/jcph.70084

Miguel Cordova-Delgado, Erika N Scott, Shahrad R Rassekh, Catrina M Loucks, Wan-Chun Chang, Edward J Raack, Jessica N Trueman, Colin J D Ross, Bruce C Carleton

{"title":"Four Pharmacogenomic Variants Strongly Linked to Corticosteroid-Induced Avascular Necrosis in Children with Cancer.","authors":"Miguel Cordova-Delgado, Erika N Scott, Shahrad R Rassekh, Catrina M Loucks, Wan-Chun Chang, Edward J Raack, Jessica N Trueman, Colin J D Ross, Bruce C Carleton","doi":"10.1002/jcph.70084","DOIUrl":"https://doi.org/10.1002/jcph.70084","url":null,"abstract":"Corticosteroids are effective anti-cancer agents for treating hematologic malignancies in children. However, avascular necrosis (AVN) is a common and debilitating adverse effect, leading to bone death and impacting long-term quality of life. This study aimed to uncover the genetic factors contributing to corticosteroid-induced AVN in a well-characterized cohort of pediatric cancer patients. We conducted a genome-wide association study (GWAS) on 972 patients, including 108 with AVN grade ≥2 and 864 dose-matched controls. The GWAS of 6.4 million genetic markers identified four significant AVN-associated loci (P < 5 × 10-8): WNT7B (OR = 9.2; 95% CI, 3.8-22.0), POGK (OR = 8.4; 95% CI, 3.6-19.5), ZNF37A (OR = 6.0; 95% CI, 2.9-12.5), and a synonymous variant in FAM240C (OR = 5.0; 95% CI, 2.6-9.5). A multi-marker predictive model combining single nucleotide polymorphisms (SNPs) and clinical factors showed an area under the ROC curve (AUC) of 78.7%, outperforming SNP-only (67.8%) and clinical-only (68.4%) models. The osteogenic processes regulated by WNT7B, part of the Wnt signaling pathway, may contribute to AVN-related disrupted bone development and repair. Similarly, POGK and ZNF37A, both containing the KRAB domain, are hypothesized to affect osteoblast differentiation and skeletal development in AVN. Developing a predictive model for individual susceptibility to corticosteroid-induced AVN will enhance the monitoring and management of corticosteroid use in children with cancer.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0