Clinical Pharmacology in Drug Development最新文献_第4页

A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy 在接受稳定美沙酮治疗的参与者中，一项评估依拉他韦和美沙酮药代动力学相互作用的一期研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-12-08 DOI: 10.1002/cpdd.1492

Randolph P. Matthews, Wendy Ankrom, Whitney Handy, Munjal Patel, Catherine Matthews, Zhiqing Xu, Kezia Gravesande, Shawn Searle, Howard Schwartz, S. Aubrey Stoch, Marian Iwamoto

{"title":"A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy","authors":"Randolph P. Matthews, Wendy Ankrom, Whitney Handy, Munjal Patel, Catherine Matthews, Zhiqing Xu, Kezia Gravesande, Shawn Searle, Howard Schwartz, S. Aubrey Stoch, Marian Iwamoto","doi":"10.1002/cpdd.1492","DOIUrl":"10.1002/cpdd.1492","url":null,"abstract":"Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1. People living with HIV-1 receiving methadone maintenance therapy may benefit from islatravir. This study was designed to evaluate single-dose islatravir on steady-state methadone pharmacokinetics. A nonrandomized, open-label study (NCT04568603) was conducted and included adult participants receiving methadone therapy. Participants received their standard methadone therapy and a single oral dose of islatravir 60 mg concomitantly. Blood samples were collected to determine methadone and islatravir pharmacokinetics. Fourteen participants aged 26-63 years were enrolled; 13 completed the study. The geometric mean ratios for methadone area under the concentration-time curve from time 0 to 24 hours (AUC0-24), maximum plasma concentration (Cmax), and concentration at 24 hours (C24) were 1.03, 1.01, and 1.07, respectively. Similar effects were seen for the R- and S-enantiomer of methadone (R-methadone: AUC0-24, 1.03; Cmax, 1.02; and C24, 1.06; S-methadone: AUC0-24, 1.03; Cmax, 1.01; and C24, 1.08). For islatravir, based on a comparison with historical data, the geometric mean ratios for AUC0-inf and Cmax were 1.18 and 0.86, respectively. Coadministration of a single dose of islatravir and methadone was generally well tolerated. Single-dose islatravir did not affect steady-state methadone pharmacokinetics in a clinically meaningful way.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"36-43"},"PeriodicalIF":1.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11701965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794164","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

Scp776, A Novel IGF-1 Fusion Protein for Acute Therapy to Promote Escape From Apoptosis in Tissues Affected by Ischemic Injury: 2 Randomized Placebo-Controlled Phase 1 Studies in Healthy Adults 一种新的IGF-1融合蛋白Scp776促进缺血损伤组织细胞凋亡的急性治疗：在健康成人中进行的2项随机安慰剂对照一期研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-12-08 DOI: 10.1002/cpdd.1486

Samuel J. Pfaff, Terry O'Reilly, Yan Zhang, Walter Olsen, Kristopher Kuchenbecker

{"title":"Scp776, A Novel IGF-1 Fusion Protein for Acute Therapy to Promote Escape From Apoptosis in Tissues Affected by Ischemic Injury: 2 Randomized Placebo-Controlled Phase 1 Studies in Healthy Adults","authors":"Samuel J. Pfaff, Terry O'Reilly, Yan Zhang, Walter Olsen, Kristopher Kuchenbecker","doi":"10.1002/cpdd.1486","DOIUrl":"10.1002/cpdd.1486","url":null,"abstract":"Apoptosis is a major driver of cell loss and infarct expansion in ischemic injuries such as acute ischemic stroke (AIS) and acute myocardial infarction (AMI). Insulin-like growth factor-1 (IGF-1) can mitigate cell death and potentiate recovery following acute ischemic injury, but short half-life and nonspecificity limit its therapeutic potential. Scp776 is an IGF-1 fusion protein designed to target damaged tissue and promote apoptosis escape and is in clinical development as an acute therapy for AIS and AMI. Two phase 1 placebo-controlled studies in healthy volunteers evaluated safety, tolerability, pharmacokinetic profile, and pharmacodynamics under single (1, 2, or 4 mg/kg) or multiple (6, 6.2, or 7.25 mg/kg total doses) dosing regimens. In addition, a blood glucose management plan was developed and implemented to mitigate hypoglycemia that may develop following scp776 injection. Scp776 was well tolerated in healthy volunteers (n = 51) without serious adverse events. Exposure increased in a near dose-proportional manner with a mean half-life across all doses of 8 hours. Adaptive dextrose infusions maintained normal blood glucose levels with occasional mild hypoglycemic events. These results informed scp776 dose selection and the design of blood glucose monitoring protocols for phase 2 studies.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"65-78"},"PeriodicalIF":1.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11701966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794177","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

At-Home Self-Collection of Pharmacokinetic Data: Design and Results From a Phase 1 Open-Label Feasibility Trial 在家自行收集药代动力学数据：1期开放标签可行性试验的设计和结果。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-12-04 DOI: 10.1002/cpdd.1495

Arash Raoufinia, Susan E. Shoaf, Brian Rothman, Chelsea Ye, Chris Chung

{"title":"At-Home Self-Collection of Pharmacokinetic Data: Design and Results From a Phase 1 Open-Label Feasibility Trial","authors":"Arash Raoufinia, Susan E. Shoaf, Brian Rothman, Chelsea Ye, Chris Chung","doi":"10.1002/cpdd.1495","DOIUrl":"10.1002/cpdd.1495","url":null,"abstract":"Pharmacokinetic (PK) studies pose unique technical challenges. We present the design of a Phase 1, open-label, fixed-sequence, PK trial that aimed to compare the timing accuracy of participant- versus staff-collected data, and we provide safety and tolerability outcomes for centanafadine treatment. Healthy adults aged 18-55 years received a single 100-mg centanafadine sustained-release tablet at Visits 1, 2, and 4. PK samples (venous sampling and blood microsampling) and safety assessments (12-lead electrocardiograms [ECGs] and vital signs) were collected by clinical site staff only at Visit 1. At Visit 2, site staff collected venous blood, and participants obtained blood microsamples, a 6-lead ECG, and vital signs under staff supervision. At Visit 4, participants obtained blood microsamples, a 6-lead ECG, and vital signs remotely. The absolute differences between actual and scheduled collection times for PK samples, ECGs, and vital signs are reported descriptively. Of the 20 participants, at least 75% obtained blood microsamples within 10 minutes of the planned nominal time. Absolute differences between actual and scheduled collection times of ECGs and vital signs were small. No adverse events were related to treatment. Overall, results support the feasibility of at-home collection of PK samples, ECGs, and vital signs.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"11-17"},"PeriodicalIF":1.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766680","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

Impact of Acid-Reducing Agents on Sotorasib Pharmacokinetics and Potential Mitigation of the Impact by Coadministration With an Acidic Beverage 降酸剂对索托拉西布药代动力学的影响以及与酸性饮料同时给药减轻影响的可能性

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-11-27 DOI: 10.1002/cpdd.1489

Panli Cardona, Natasha Strydom, Brett Houk

{"title":"Impact of Acid-Reducing Agents on Sotorasib Pharmacokinetics and Potential Mitigation of the Impact by Coadministration With an Acidic Beverage","authors":"Panli Cardona, Natasha Strydom, Brett Houk","doi":"10.1002/cpdd.1489","DOIUrl":"10.1002/cpdd.1489","url":null,"abstract":"Sotorasib exhibits pH-dependent solubility, making it susceptible to altered exposures when coadministered with acid-reducing agents (ARAs). Several clinical studies were conducted to investigate the impact of ARAs on sotorasib pharmacokinetics under different clinically relevant scenarios and to identify potential mitigation strategies. Upon coadministration of 960 mg of sotorasib and 40 mg of omeprazole under fasted conditions, sotorasib area under the concentration-time curve (AUC) and maximum observed plasma concentration (Cmax) decreased approximately 42% and 57%, respectively. Following coadministration with 40 mg of famotidine under fed conditions, sotorasib AUC and Cmax decreased approximately 38% and 35%, respectively. The coadministration of sotorasib and 40 mg of omeprazole under fed conditions led to a 57% and 65% decrease in sotorasib AUC and Cmax, respectively. When sotorasib was coadministered with omeprazole and an acidic beverage compared to sotorasib alone, AUC and Cmax decreased approximately 23% and 32%, respectively, leading to a 19.0 percentage-point increase in AUC and a 24.6 percentage-point increase in Cmax for sotorasib when compared to coadministration of sotorasib with omeprazole under fasted conditions. Sotorasib exposure decreased when coadministered with proton pump inhibitors and H2 receptor antagonists. Coadministration with an acidic beverage increased sotorasib exposure upon concomitant administration with omeprazole, which may represent a clinically attractive method to allow ARA use with sotorasib.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 2","pages":"167-176"},"PeriodicalIF":1.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738675","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

Phase 1, Single-Center, Double-Blind, Randomized, Placebo-Controlled Studies of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of the Sirtuin 6 Activator SP-624 in Healthy Adults 关于健康成人单剂量和多剂量口服 Sirtuin 6 激活剂 SP-624 的安全性、耐受性和药代动力学的 1 期单中心、双盲、随机、安慰剂对照研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-11-26 DOI: 10.1002/cpdd.1488

Greg Rigdon, Yuki Prescott, John Hall, Kelly Abernathy, Joel Raskin, William Wargin

{"title":"Phase 1, Single-Center, Double-Blind, Randomized, Placebo-Controlled Studies of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of the Sirtuin 6 Activator SP-624 in Healthy Adults","authors":"Greg Rigdon, Yuki Prescott, John Hall, Kelly Abernathy, Joel Raskin, William Wargin","doi":"10.1002/cpdd.1488","DOIUrl":"10.1002/cpdd.1488","url":null,"abstract":"Sirtuin 6 activation is a novel epigenetic mechanism proposed for treatment of depression. Two Phase 1 studies, SP-624-101 and SP-624-102, examined the pharmacokinetics and safety of SP-624, an orally active sirtuin 6 activator, in healthy adults. SP-624-101 was a single-ascending-dose study. In Part A, participants were randomized 6:2 to SP-624 (single oral doses of 3, 10, or 30 mg) or placebo. Part B compared results in 8 participants receiving SP-624 while fasting or after a high-fat, high-calorie breakfast. In SP-624-102, a multiple-ascending-dose study, participants were randomized 6:2 to SP-624 (3 or 10 mg SP-624 daily) or placebo for 5 days and 5:2 to SP-624 20 mg daily or placebo for 10 days. At all doses, maximum concentration (Cmax) exceeded predicted target plasma concentrations of 3.28 ng/mL. Area under the concentration-time curve and Cmax increased dose proportionally. A food effect resulted in significantly lower Cmax, later time to maximum concentration, and comparable AUC for fed versus fasting participants. No serious adverse events were observed. In SP-624-101 and SP-624-102, respectively, 3 (12%) and 5 (29%) SP-624–treated participants experienced treatment-emergent adverse events. SP-624 was well tolerated and reached target concentrations in healthy adults, supporting progression of SP-624 20 mg daily into Phase 2 studies of major depressive disorder.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"18-25"},"PeriodicalIF":1.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11701958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715584","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

Pharmacokinetics and Bioequivalence Evaluation of Trazodone Hydrochloride Sustained-Release Tablets in Healthy Chinese Volunteers 健康中国志愿者服用盐酸曲唑酮缓释片的药代动力学和生物等效性评价

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-11-25 DOI: 10.1002/cpdd.1490

Jingyan Wang, Yuan Xu, Zhicheng Zhao, Tian Meng, Yang Zou, Yi Lan

{"title":"Pharmacokinetics and Bioequivalence Evaluation of Trazodone Hydrochloride Sustained-Release Tablets in Healthy Chinese Volunteers","authors":"Jingyan Wang, Yuan Xu, Zhicheng Zhao, Tian Meng, Yang Zou, Yi Lan","doi":"10.1002/cpdd.1490","DOIUrl":"10.1002/cpdd.1490","url":null,"abstract":"The aim of this study was to investigate the pharmacokinetics, bioequivalence, and safety of generic trazodone hydrochloride sustained-release tablet and its reference listed product in healthy Chinese subjects. An open, randomized, single-dose, and 2-period crossover study was involved under fasting and fed conditions, with a 7-day washout period. A single oral dose of 150 mg of 2 trazodone hydrochloride sustained-release tablets was administered to 84 healthy volunteers, with 36 in the fasting group and 48 consuming a high-fat diet, respectively. The plasma concentrations of trazodone were analyzed using a liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters were obtained from concentration-time profiles. The geometric mean ratio with 90% confidence intervals of the maximum trazodone concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the bioequivalence acceptance criteria (80%-125%) under fasting and fed conditions, which indicated that the test and reference formulations were bioequivalent. Compared with the fasting study, the concomitant administration of trazodone with a high-fat diet had a negligible influence on the drug pharmacokinetic behavior. Adverse events were recorded, and no serious adverse events were observed during either fasting or fed conditions. Trazodone has proven to have an acceptable safety profile in the Chinese population, with bioequivalence successfully established under both fasting and fed conditions.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 2","pages":"177-183"},"PeriodicalIF":1.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715583","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

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Neonatal Fc Receptor Inhibitor Rozanolixizumab: An Ethnic Sensitivity Study in Healthy Japanese, Chinese, and White Participants 新生儿 Fc 受体抑制剂 Rozanolixizumab 的安全性、耐受性、药代动力学和药效学：健康日本人、中国人和白人参与者的种族敏感性研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-11-21 DOI: 10.1002/cpdd.1484

Assem el Baghdady, Rocío Lledó-García, Maryam Gayfieva, Romana Lowcock, Shikiko Watanabe, Jagdev Sidhu, Denisa Wilkes

{"title":"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Neonatal Fc Receptor Inhibitor Rozanolixizumab: An Ethnic Sensitivity Study in Healthy Japanese, Chinese, and White Participants","authors":"Assem el Baghdady, Rocío Lledó-García, Maryam Gayfieva, Romana Lowcock, Shikiko Watanabe, Jagdev Sidhu, Denisa Wilkes","doi":"10.1002/cpdd.1484","DOIUrl":"10.1002/cpdd.1484","url":null,"abstract":"Rozanolixizumab is an anti-human neonatal Fc receptor humanized immunoglobulin (Ig) G4 monoclonal antibody that reduces IgG, including pathogenic IgG autoantibodies. Rozanolixizumab safety and tolerability have been assessed in previous clinical studies with predominantly White participants. We assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of rozanolixizumab in healthy Japanese and Chinese participants compared with White participants. This double-blind, single-center, UK-based, Phase 1 study randomized 65 participants to rozanolixizumab 4 mg/kg (Japanese and White participants only), 7 mg/kg, or 10 mg/kg. All treatment-emergent adverse events (TEAEs) were mild to moderate in severity; no severe TEAEs, serious TEAEs, or TEAEs leading to discontinuation occurred. Incidences of TEAEs in Japanese and Chinese participants were comparable to those in White participants. Japanese and Chinese participants had lower systemic rozanolixizumab exposure relative to Caucasian participants, attributable to lower actual doses administered due to lower body weight in Chinese and Japanese participants, indicating that body weight is not a relevant predictor of rozanolixizumab pharmacokinetics. All 3 ethnicities demonstrated dose-dependent IgG reductions, with IgG nadir achieved around Day 10 and gradual return to baseline levels by Day 56. These data support the applicability of safety data from previous clinical studies of rozanolixizumab to individuals of Japanese and Chinese ethnicity.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"26-35"},"PeriodicalIF":1.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681079","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

The Safety, Tolerability, and Pharmacokinetics of Active Ingredients From Hydroxysafflor Yellow A in Healthy Chinese Volunteers 中国健康志愿者对羟基红花黄色素 A 活性成分的安全性、耐受性和药代动力学研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-11-17 DOI: 10.1002/cpdd.1487

Xiuli Zhao, Shanye Gu, Xia wang, Yefeng Cai, Ziyi Zhou

{"title":"The Safety, Tolerability, and Pharmacokinetics of Active Ingredients From Hydroxysafflor Yellow A in Healthy Chinese Volunteers","authors":"Xiuli Zhao, Shanye Gu, Xia wang, Yefeng Cai, Ziyi Zhou","doi":"10.1002/cpdd.1487","DOIUrl":"10.1002/cpdd.1487","url":null,"abstract":"Hydroxysafflor yellow A (HSYA), an active ingredient extracted from Carthami flos, shows potential for treating ischemic stroke. This phase 1 study assessed the safety, tolerability, and pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers who received intravenous infusions of pure HSYA powder. The study comprised 2 parts. Part A was a randomized, double-blind, placebo-controlled dose-escalation study that evaluated safety and tolerability. This included a single-dose study with 7 dose levels of HSYA (6.25, 12.5, 25, 50, 75, 100, and 125 mg) in 52 volunteers, and a multidose study (100 and 125 mg) in 16 volunteers. Part B was an open-label study where 12 volunteers received 75 mg of HSYA once daily for 14 consecutive days to examine PKs. There were no adverse events (AEs) leading to treatment discontinuation by HSYA throughout the treatment period. All reported AEs were mild and did not require special treatment. PK analysis revealed rapid absorption (median Tmax of 1.1 hours) and elimination (median t1/2 4.0 and 4.7 hours) of HSYA. Total body clearance on the 1st and 14th days was 1.7 and 1.6 L/h, respectively.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"79-86"},"PeriodicalIF":1.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647072","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

Pharmacokinetics and Bioequivalence of Two Formulations of Montelukast Sodium Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions 空腹和进食条件下两种配方的孟鲁司特钠片剂在健康中国志愿者中的药代动力学和生物等效性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-11-13 DOI: 10.1002/cpdd.1485

Xiali Rao, Xinghong Wu, Jiawei Hu, Zhaoming Huang

{"title":"Pharmacokinetics and Bioequivalence of Two Formulations of Montelukast Sodium Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions","authors":"Xiali Rao, Xinghong Wu, Jiawei Hu, Zhaoming Huang","doi":"10.1002/cpdd.1485","DOIUrl":"10.1002/cpdd.1485","url":null,"abstract":"Montelukast sodium is a leukotriene type 1 receptor antagonist that can be used for the prophylaxis and treatment of asthma. However, the pharmacokinetics of montelukast sodium tablets (10 mg) remain unclear in healthy Chinese subjects. Here, a single-dose randomized, open-label, 2-sequence, and 2-period crossover (7-day washout period between treatments) study was performed to compare the pharmacokinetics and bioequivalence between the test products and the reference at a single dose of 10 mg among healthy Chinese subjects under fasting and fed conditions. Blood samples were collected at specified time points to analyze the plasma concentrations of montelukast by a validated liquid chromatography-tandem mass spectrometry method. The results showed that the 90% confidence interval values of the geometric mean ratio of test/reference for the maximum plasma drug concentration, area under the concentration-time curve from time 0 to the end, and area under the concentration-time curve from time 0 to infinity were within the range of 80%-125%. Moreover, both the test and reference formulations were safe and well tolerated, with no occurrence of severe adverse events. These results demonstrate that both the test montelukast sodium tablets and the reference showed similar bioequivalence, safety, and tolerability among healthy Chinese subjects under fasting and fed conditions.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 2","pages":"161-166"},"PeriodicalIF":1.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615440","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 Efficacy and Safety in Treating Epidermal Growth Factor Receptor Mutation-Positive Advanced Non–Small-Cell Lung Cancer: A Meta-Analysis 奥希替尼治疗表皮生长因子受体突变阳性晚期非小细胞肺癌的有效性和安全性：一项 Meta 分析。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-11-08 DOI: 10.1002/cpdd.1483

Mengmeng Zhao, Jian Zhang, Jie Gao, Jianping Wang, Zhenkai Ma

{"title":"Osimertinib Efficacy and Safety in Treating Epidermal Growth Factor Receptor Mutation-Positive Advanced Non–Small-Cell Lung Cancer: A Meta-Analysis","authors":"Mengmeng Zhao, Jian Zhang, Jie Gao, Jianping Wang, Zhenkai Ma","doi":"10.1002/cpdd.1483","DOIUrl":"10.1002/cpdd.1483","url":null,"abstract":"This study compared the safety and efficacy of osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), with those of other TKIs and its use alongside bevacizumab in patients with EGFR mutation-positive advanced non–small-cell lung cancer. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were used to conduct extensive searches for relevant randomized controlled trials until January 30, 2024. Osimertinib monotherapy favored disease control rate, whereas the comparator treatment arm favored overall survival. Using subgroup analysis, the objective response rate and progression-free survival (PFS) were significantly elevated by Osimertinib monotherapy compared with pemetrexed combined with carboplatin or cisplatin. The comparator treatment arm receiving gefitinib or erlotinib significantly favored progression-free survival and overall survival compared with osimertinib monotherapy. In patients treated with osimertinib monotherapy, the incidence of all adverse events (AEs) decreased compared with comparator treatment arm. Anemia was the only AE associated with osimertinib monotherapy. Pemetrexed combined with carboplatin or cisplatin resulted in greater loss of appetite than osimertinib monotherapy. The most associated AE of osimertinib monotherapy was diarrhea, according to network analysis. Although its efficacy is not consistent with other EGFR TKIs, osimertinib was associated with a decrease in AEs in patients with EGFR mutation-positive advanced non–small-cell lung cancer.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 1","pages":"5-10"},"PeriodicalIF":1.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615431","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