Clinical Pharmacology in Drug Development最新文献_第3页

Clinical Evaluation of Potential Interaction Between Bemnifosbuvir and Ruzasvir With an Assessment of Food Effect: Results of a Phase 1 Study in Healthy Participants. 贝尼非布韦和鲁扎韦潜在相互作用与食物效应评估的临床评价：健康参与者的1期研究结果

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-24 DOI: 10.1002/cpdd.1540

Xiao-Jian Zhou, Gaetano Morelli, Maureen Montrond, Shannan Lynch, Keith Pietropaolo, Bruce Belanger, Arantxa Horga, Janet Hammond

{"title":"Clinical Evaluation of Potential Interaction Between Bemnifosbuvir and Ruzasvir With an Assessment of Food Effect: Results of a Phase 1 Study in Healthy Participants.","authors":"Xiao-Jian Zhou, Gaetano Morelli, Maureen Montrond, Shannan Lynch, Keith Pietropaolo, Bruce Belanger, Arantxa Horga, Janet Hammond","doi":"10.1002/cpdd.1540","DOIUrl":"https://doi.org/10.1002/cpdd.1540","url":null,"abstract":"A combination of nucleotide hepatitis C virus (HCV) nonstructural protein (NS) 5B and 5A inhibitors is a preferred standard of care for treating chronic HCV. Bemnifosbuvir is a novel oral guanosine nucleotide prodrug with potent pan-genotypic inhibitory activity against HCV NS5B. Ruzasvir, a small-molecule NS5A inhibitor, has demonstrated improved anti-HCV activity compared with first-generation NS5A inhibitors. Clinical studies have demonstrated favorable efficacy and safety of bemnifosbuvir and ruzasvir in combination with other NS5A and NS5B inhibitors, respectively. A Phase 1 study in healthy participants was conducted to assess the drug-drug interaction potential between bemnifosbuvir and ruzasvir, as well as food effects following coadministration of both compounds. Under fasted conditions, the peak, trough, and total exposure to bemnifosbuvir and its metabolites were increased upon coadministration with ruzasvir (by a maximum of 33% vs bemnifosbuvir alone), whereas the corresponding values for ruzasvir were decreased upon coadministration with bemnifosbuvir (by a maximum of 26% vs ruzasvir alone). Food delayed peak exposure to both drugs (by up to 2 hours) while increasing their peak and total exposure by up to 63%. No serious adverse events or premature drug discontinuations were reported. Overall, the study results support further evaluation of bemnifosbuvir and ruzasvir combination therapy for treating chronic HCV.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978584","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

A Phase I Study to Evaluate the Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Adults with Renal Impairment. 一项评估成人肾脏损害患者PDE5抑制剂TPN171的药代动力学和安全性的I期研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-21 DOI: 10.1002/cpdd.1536

Ping Fu, Yi Song, Chao Hu, Xiaolan Yong, Yang Yu, Yi Chen, Ying Wang, Xiaohong Zhu, Zhen Wang, Yu Wang, Jiaxiang Juan, Yuan Chen, Jia Miao

{"title":"A Phase I Study to Evaluate the Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Adults with Renal Impairment.","authors":"Ping Fu, Yi Song, Chao Hu, Xiaolan Yong, Yang Yu, Yi Chen, Ying Wang, Xiaohong Zhu, Zhen Wang, Yu Wang, Jiaxiang Juan, Yuan Chen, Jia Miao","doi":"10.1002/cpdd.1536","DOIUrl":"https://doi.org/10.1002/cpdd.1536","url":null,"abstract":"TPN171, a phosphodiesterase 5 inhibitor, is under development for the treatment of male erectile dysfunction and pulmonary arterial hypertension in China. To investigate the pharmacokinetic properties and safety of TPN171 in individuals with severe renal impairment and normal renal function, an open-label, single-dose, parallel-group phase 1 study was conducted in 8 participants with severe renal impairment (glomerular filtration rate within 15-29 mL/min) and 8 participants having normal renal function, who received TNP171 tablets (10 mg) in the fasting state. As compared with those with normal renal function, the geometric mean ratios for maximum plasma concentration (Cmax), the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t), and AUC extrapolated to infinite time (AUC0-∞) were 74.3%, 138%, and 137%, respectively. Elimination half-life was prolonged and clearance was decreased in severe renal impairment group. The adverse reaction rate showed no significant difference. All adverse events were mild intensity, and no participant was discontinued in this study. In conclusion, TPN171 can be cautiously used in patients with mild to severe renal impairment.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985544","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

Comparative Bioequivalence Study of 2 Fixed-Dose Combinations of Vildagliptin and Metformin at a Tablet Strength of 50/1000 mg in Moroccan Volunteers. 维格列汀和二甲双胍两种固定剂量组合片剂强度为50/ 1000mg在摩洛哥志愿者中的生物等效性比较研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-21 DOI: 10.1002/cpdd.1528

Salma Lazrak, Oumaima Ouaouda, Jalal Bektachi, Mohamed Ali Iraqi, Choukri El Khabbaz, Yahya Cherrah

{"title":"Comparative Bioequivalence Study of 2 Fixed-Dose Combinations of Vildagliptin and Metformin at a Tablet Strength of 50/1000 mg in Moroccan Volunteers.","authors":"Salma Lazrak, Oumaima Ouaouda, Jalal Bektachi, Mohamed Ali Iraqi, Choukri El Khabbaz, Yahya Cherrah","doi":"10.1002/cpdd.1528","DOIUrl":"https://doi.org/10.1002/cpdd.1528","url":null,"abstract":"This study evaluates the bioequivalence of 2 fixed-dose combinations of vildagliptin (50 mg) and metformin (1000 mg) in healthy Moroccan volunteers. A single-dose, randomized, simple-blind, 2-sequence, 2-period crossover design was conducted with 30 participants, 28 of whom completed the study. The test product was compared to the reference product (by measuring pharmacokinetic parameters, including maximum plasma concentration, area under the concentration-time curve (AUC) from time zero to the last measurable time point, AUC from time zero extrapolated to infinity, and time to maximum concentration. Blood samples were collected at predefined intervals after dosing, and plasma concentrations of vildagliptin and metformin were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic analysis showed comparable results between the 2 formulations. Both products met the bioequivalence criteria of 80%-125% for maximum plasma concentration and AUC. Safety assessments revealed no serious adverse events, and both products were well tolerated. The study concluded that the test product is bioequivalent to the reference, supporting its therapeutic interchangeability in managing type 2 diabetes mellitus.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955288","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

A Phase 1 Study to Evaluate the Absorption, Metabolism, and Disposition of Dordaviprone in Healthy Adult Participants. 一项评估健康成年参与者中Dordaviprone的吸收、代谢和处置的一期研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-17 DOI: 10.1002/cpdd.1541

Yohannes Teffera, Tim Tippin, Angela Bartkus, Francine A de Castro, Shamia L Faison, Marion Morrison, Mark J Mullin, Odin Naderer

{"title":"A Phase 1 Study to Evaluate the Absorption, Metabolism, and Disposition of Dordaviprone in Healthy Adult Participants.","authors":"Yohannes Teffera, Tim Tippin, Angela Bartkus, Francine A de Castro, Shamia L Faison, Marion Morrison, Mark J Mullin, Odin Naderer","doi":"10.1002/cpdd.1541","DOIUrl":"https://doi.org/10.1002/cpdd.1541","url":null,"abstract":"Dordaviprone (ONC201) is a novel, small-molecule imipridone with antitumor activity in patients with a glioma. Six healthy male participants received a single 625-mg (100-µCi) oral dose of [14C]-dordaviprone. Blood, plasma, urine, and feces were collected up to 288 hours after dosing and analyzed by liquid scintillation counting. Metabolite profiles were evaluated using liquid chromatography-radiometric detection, and metabolite identification was accomplished by liquid chromatography with tandem mass spectrometry. Concentrations of drug-derived radioactivity in blood and plasma peaked at 1 hour after dosing and were below the limit of quantitation by 72 hours (whole blood) to 96 hours (plasma) after dosing. Seventy-one percent of the administered radioactivity was recovered in urine and 20% in feces. In plasma, the major circulating compounds were dordaviprone and the inactive metabolite ONC207, each contributing approximately one third of the total radioactivity area under the curve. Of the 19 metabolites identified in plasma, no other single metabolite contributed more than 10% to the total radioactivity area under the curve. Unchanged dordaviprone was a minor component in excreta (less than 0.3%), with multiple metabolites identified in urine and feces. Given the lack of dordaviprone in excreta and the metabolites formed, the primary route for dordaviprone elimination was through urinary excretion of oxidative metabolites.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970960","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

A Phase 1C, Open Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of DM199 Administered Intravenously with a Polyvinyl Chloride Bag in Adult Healthy Subjects and Adults Recently Taking Angiotensin-Converting Enzyme Inhibitors. 一项1C期、开放标签、单次递增剂量研究，评估成年健康受试者和近期服用血管紧张素转换酶抑制剂的成年人用聚乙烯袋静脉注射DM199的安全性、耐受性和药代动力学。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-16 DOI: 10.1002/cpdd.1534

Michael Giuffre, Annette D Lista, Nick Paulson, Lorianne Masuoka

{"title":"A Phase 1C, Open Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of DM199 Administered Intravenously with a Polyvinyl Chloride Bag in Adult Healthy Subjects and Adults Recently Taking Angiotensin-Converting Enzyme Inhibitors.","authors":"Michael Giuffre, Annette D Lista, Nick Paulson, Lorianne Masuoka","doi":"10.1002/cpdd.1534","DOIUrl":"https://doi.org/10.1002/cpdd.1534","url":null,"abstract":"This small phase 1C, open-label, single ascending dose study evaluated the safety, tolerability, and pharmacokinetics (PKs) of DM199, a recombinant form of human tissue kallikrein-1 (KLK1). A small sample size of both healthy subjects and hypertensive adults recently taking angiotensin-converting enzyme inhibitors was studied. KLK1 has a known role in vasodilation and blood flow regulation, with potential implications for treatment of acute ischemic stroke (AIS) by focally enhancing cerebral perfusion. A total of 12 subjects were enrolled; 9 healthy subjects received escalating doses of DM199 (0.1-0.5 µg/kg), while 3 hypertensive subjects received the maximum tolerated dose of 0.5 µg/kg. Safety assessments indicated that DM199 was well tolerated, with mild adverse events reported, such as headache and flushing. No infusion-related hypotensive events occurred, and all subjects completed the study without significant clinical issues. The study was performed following prior PK analyses revealing that DM199 exposure was greater when administered with polyvinyl chloride infusion materials compared with polyolefin infusion materials. This study supports a revised dosing strategy for DM199 in the ongoing ReMEDy2 trial for AIS and highlights the need for careful consideration of the risk-benefit profile in the clinical context of AIS treatment.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977336","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 Safety of a Fixed-Dose Combination of Alogliptin and Extended-Release Metformin Under Fasting and/or Fed Conditions in Healthy Adults. 健康成人空腹和/或非空腹进食条件下阿格列汀和缓释二甲双胍固定剂量联合用药的药代动力学和安全性

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-04-16 DOI: 10.1002/cpdd.1532

Ji Hye Song, Jae Hoon Kim, Jang Hee Hong, Jin-Gyu Jung, Sun Young Park, Jung Sunwoo

{"title":"Pharmacokinetics and Safety of a Fixed-Dose Combination of Alogliptin and Extended-Release Metformin Under Fasting and/or Fed Conditions in Healthy Adults.","authors":"Ji Hye Song, Jae Hoon Kim, Jang Hee Hong, Jin-Gyu Jung, Sun Young Park, Jung Sunwoo","doi":"10.1002/cpdd.1532","DOIUrl":"https://doi.org/10.1002/cpdd.1532","url":null,"abstract":"This phase 1, randomized, open-label, 2 × 2 crossover study evaluated the bioequivalence of fixed-dose combination (FDC) formulations of alogliptin (ALO) and metformin extended-release (MET XR) compared to their individual formulations and assessed the effect of food on FDC pharmacokinetics in healthy participants. The study comprised the high-dose bioequivalence study (ALO 25 mg/MET XR 1000 mg) and the low-dose bioequivalence study (ALO 12.5 mg/MET XR 500 mg), both conducted under fasting conditions, and the food effect study (ALO 12.5 mg/MET XR 1000 mg) conducted under both fasting and fed conditions. Among enrolled participants, 46 of 50 completed the high-dose bioequivalence study, 45 of 51 completed the low-dose bioequivalence study, and 22 of 26 completed the food effect study. Plasma concentrations were analyzed using liquid chromatography-tandem mass spectrometry. The geometric mean ratios of AUClast and Cmax for the FDC versus individual formulations were within the bioequivalence range (0.80-1.25) for both ALO and MET XR. ALO's pharmacokinetics were unaffected by food, while MET XR exhibited a significant food effect, with AUClast increasing by a factor of 1.63 and Tmax delayed by 2 hours. Given these findings, the FDC should be administered with food, consistent with MET XR monotherapy recommendations.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994485","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 of Butylphthalide Injection in Elderly Chinese Patients With Ischemic Stroke 丁苯酞注射液在中国老年缺血性脑卒中患者中的人群药代动力学。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-03-28 DOI: 10.1002/cpdd.1525

Shu-Xian Lyu, Xue-Yan Cui, Shi-Xian Chen, Hai-yan Shi, Xin Huang

{"title":"Population Pharmacokinetics of Butylphthalide Injection in Elderly Chinese Patients With Ischemic Stroke","authors":"Shu-Xian Lyu, Xue-Yan Cui, Shi-Xian Chen, Hai-yan Shi, Xin Huang","doi":"10.1002/cpdd.1525","DOIUrl":"10.1002/cpdd.1525","url":null,"abstract":"Butylphthalide is widely used to treat acute ischemic stroke in China, and the main adverse effect is the increase in transaminase levels. We aimed to establish a population pharmacokinetic model of butylphthalide in elderly patients with ischemic stroke and identified covariates influencing butylphthalide pharmacokinetics. We collected butylphthalide blood samples via opportunistic sampling. We chose the base model, compared 1-, 2-, and 3-compartment models, and used basic patient information, laboratory test results, concomitant drugs, and comorbidities as covariates to examine our study. Our study included 50 patients (n = 106 blood samples), and a 2-compartment model with first-order elimination matched the experimental data well. Body weight and comorbid diabetes significantly affect the clearance of butylphthalide. On the basis of the final PPK model, the Monte Carlo method was used to compare the effects of different body weights and the state of diabetes on the steady-state area under the concentration–time curve at 0-24 hours. The results revealed that the steady-state area under the concentration–time curve at 0-24 hours was lower in patients with diabetes than in patients without diabetes, and both values decreased with weight gain. Our findings provide information for personalized treatment plans for patients with ischemic stroke (aged 65 years or older) receiving butylphthalide injection.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 5","pages":"360-367"},"PeriodicalIF":1.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735958","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

Physiologically Based Pharmacokinetic Modeling to Predict Drug–Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P–Glycoprotein Inhibition 基于生理的药代动力学模型预测索替列司他作为CYP诱导和抑制的受害者，以及作为CYP和p糖蛋白抑制的犯罪者的药物-药物相互作用。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-03-27 DOI: 10.1002/cpdd.1526

Hongxia Jia, T. Eric Ballard, Liming Zhang, Lawrence Cohen, Mackenzie C. Bergagnini-Kolev, Ian E. Templeton, Hannah M. Jones, Wei Yin

{"title":"Physiologically Based Pharmacokinetic Modeling to Predict Drug–Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P–Glycoprotein Inhibition","authors":"Hongxia Jia, T. Eric Ballard, Liming Zhang, Lawrence Cohen, Mackenzie C. Bergagnini-Kolev, Ian E. Templeton, Hannah M. Jones, Wei Yin","doi":"10.1002/cpdd.1526","DOIUrl":"10.1002/cpdd.1526","url":null,"abstract":"Soticlestat (TAK-935) is a cholesterol 24-hydroxylase inhibitor. A physiologically-based pharmacokinetic model has been developed to predict potential soticlestat drug–drug interactions (DDIs) using the Simcyp v20 Population-based Simulator and verified with data from single-/multiple-rising-dose and clinical DDI studies. Simulated area under the plasma concentration–time curve from 0 to infinity (AUC0-inf) and maximal drug concentration (Cmax) based on the model were generally within 2-fold of observed values for all soticlestat doses. Model-simulated versus observed AUC0-inf and Cmax geometric mean ratios (GMRs) for soticlestat with/without itraconazole (potent cytochrome P450 [CYP] 3A inhibitor), and mefenamic acid (potent UDP glucuronosyltransferase [UGT] 1A9 inhibitor) were ≤1.10-fold. As soticlestat is primarily metabolized by UGT enzymes and Simulator v20 incorporates rifampin's induction of CYP3A only, the model underpredicted soticlestat's DDI with rifampin. However, with user-defined rifampin UGT induction, the predicted AUC0-inf GMR was within 1.5-fold of the observed value, meeting the 2-fold acceptance criteria. Hence, the model was appropriate for evaluating DDIs with CYP3A inhibitors and inducers not evaluated in clinical DDI studies; all predicted DDIs were low/not clinically relevant (<50% impact on exposure). Furthermore, no clinically significant DDIs were predicted following coadministration of soticlestat with sensitive CYP2C8, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein substrates.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 5","pages":"368-381"},"PeriodicalIF":1.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718270","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

Target-Mediated Modeling of Alirocumab in Adolescents and Children ≥8 to <12 Years of Age Using Phase II and III Data 使用II期和III期数据，Alirocumab在≥8至<12岁的青少年和儿童中的靶向介导模型

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-03-26 DOI: 10.1002/cpdd.1523

Pavel Kovalenko, Lutz Harnisch, Jeanne Mendell, Yuhuan Wang, John D. Davis, Albert Thomas DiCioccio

{"title":"Target-Mediated Modeling of Alirocumab in Adolescents and Children ≥8 to <12 Years of Age Using Phase II and III Data","authors":"Pavel Kovalenko, Lutz Harnisch, Jeanne Mendell, Yuhuan Wang, John D. Davis, Albert Thomas DiCioccio","doi":"10.1002/cpdd.1523","DOIUrl":"10.1002/cpdd.1523","url":null,"abstract":"A population pharmacokinetic (PK) covariate analysis was conducted utilizing data from adolescents and children ≥8 to <12 years of age with heterozygous familial hypercholesterolemia. One phase II and 1 phase III study were analyzed (121 patients on active treatment). A 2-compartment target-mediated model with linear and target-mediated elimination and transit compartments describing lag time in absorption was utilized. Weight and high-dose statins were statistically significant covariate. Except for the central volume, estimated population PK parameters describing linear kinetics were similar across pediatric patients and healthy adults. Coadministration of concomitant high doses of statins was associated with an increase in the production rate of proprotein convertase subtilisin/kexin type 9. The primary covariate model adequately described alirocumab PKs in the pediatric population. The analysis supports the recommended weight-adjusted subcutaneous dosing regimens for alirocumab in children with heterozygous hypercholesterolemia aged ≥8 years.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 5","pages":"347-359"},"PeriodicalIF":1.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708817","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

CPDD 2024 Reviewer List CPDD 2024审稿人名单。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-03-04 DOI: 10.1002/cpdd.1524

引用次数: 0