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

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":"https://doi.org/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":" ","pages":""},"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

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":"https://doi.org/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":" ","pages":""},"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

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":"https://doi.org/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":" ","pages":""},"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

Relative Bioavailability Studies With Mitapivat: Formulation and Food Effect Assessments in Healthy Subjects 米达必瓦特的相对生物利用度研究：健康受试者的配方和食物效应评估。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-25 DOI: 10.1002/cpdd.1481

Varsha Iyer, Karen Sullivan, Yan Yan, Peter Hawkins

{"title":"Relative Bioavailability Studies With Mitapivat: Formulation and Food Effect Assessments in Healthy Subjects","authors":"Varsha Iyer, Karen Sullivan, Yan Yan, Peter Hawkins","doi":"10.1002/cpdd.1481","DOIUrl":"10.1002/cpdd.1481","url":null,"abstract":"Pyruvate kinase (PK) deficiency is a rare, hereditary, hemolytic anemia caused by mutations in the PKLR gene encoding the PK enzyme. Mitapivat (previously designated AG-348) is a first-in-class, oral, allosteric activator of PK. We report results from 5 Phase 1 trials in healthy adults to characterize and compare mitapivat pharmacokinetics across different formulations and analyze food effects on mitapivat bioavailability (Studies 1-5). Pharmacokinetic assessments were peak exposure, total exposure, time to maximum plasma concentration of mitapivat, and relative bioavailability (where appropriate). Plasma total exposure of mitapivat was similar in the fasted and fed (high-fat meal or different soft foods) states after capsule, tablet, and pediatric granule formulations. Although mitapivat administration with food reduced the rate of mitapivat absorption (delay in time to maximum plasma concentration; reduction in maximum concentration) versus dosing under fasted conditions, this was not considered clinically relevant, given the lack of effect on total mitapivat exposure. Consequently, the administration instructions for mitapivat relating to food state that “patients may take mitapivat tablets with or without food.” These findings will continue to inform clinical studies and development of mitapivat in adult and pediatric patients with hemolytic anemias and may help inform healthcare professionals on mitapivat dosing/administration recommendations in clinical practice.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1271-1282"},"PeriodicalIF":1.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496444","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 2 Oral Formulations of Vildagliptin in Healthy Chinese Subjects. 维达列汀两种口服制剂在中国健康受试者中的药代动力学和生物等效性研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-24 DOI: 10.1002/cpdd.1482

Mengli Tian, Libing Ye, Binhong Liang, Yingrong Chen, Jue Mei, Zhouming Zhao, Xiaodi Guo, Min Xu, Jingyao Zhang, Shuixin Yang

{"title":"Pharmacokinetics and Bioequivalence of 2 Oral Formulations of Vildagliptin in Healthy Chinese Subjects.","authors":"Mengli Tian, Libing Ye, Binhong Liang, Yingrong Chen, Jue Mei, Zhouming Zhao, Xiaodi Guo, Min Xu, Jingyao Zhang, Shuixin Yang","doi":"10.1002/cpdd.1482","DOIUrl":"https://doi.org/10.1002/cpdd.1482","url":null,"abstract":"A randomized, open-label, 2-period, 2-sequence crossover study was conducted to evaluate the pharmacokinetics and bioequivalence of 2 oral formulations of vildagliptin tablets under both fasting and fed conditions in healthy Chinese subjects. A total of 56 healthy subjects were randomized to receive a single 50-mg dose of either a generic vildagliptin tablet (T) or the reference formulation (R). The washout period was 3 days. Blood samples were collected up to 24 hours postdosing during each period and analyzed for vildagliptin using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The 90% confidence intervals for the geometric mean ratios (T:R) of maximum serum concentration, area under the serum concentration-time curve from time 0 to the last measurable concentration, and area under the serum concentration-time curve from time 0 to infinity were all within the predefined bioequivalence range of 80%-125%. This indicates that the generic and reference formulations are bioequivalent under both fasting and fed states. All adverse events reported were mild and transient. High-fat meals delayed absorption and reduced the maximum peak concentration of both formulations; however, they did not affect the overall exposure. Therefore, vildagliptin can be taken without regard to meals.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496443","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

Bioequivalence and Pharmacokinetic Evaluation of Regorafenib Tablets in Healthy Chinese Volunteers 瑞戈非尼片在中国健康志愿者中的生物等效性和药代动力学评价

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-23 DOI: 10.1002/cpdd.1474

Zhaoyu Wang, Yun Zhang, Jingjing Liu, Xijing Chen

{"title":"Bioequivalence and Pharmacokinetic Evaluation of Regorafenib Tablets in Healthy Chinese Volunteers","authors":"Zhaoyu Wang, Yun Zhang, Jingjing Liu, Xijing Chen","doi":"10.1002/cpdd.1474","DOIUrl":"10.1002/cpdd.1474","url":null,"abstract":"This was a single-center, randomized, open-label, 2-formulation, and 2-cycle crossover trial conducted in 48 healthy Chinese volunteers, under fasting and fed conditions. The participants received oral doses of the test formulation (regorafenib) and reference formulation (40 mg) during each study period. Blood samples were collected before and up to 144 hours after the formulations were administered to determine changes in the pharmacokinetic parameters and adverse reactions, which were then used to evaluate bioequivalence and safety. The geometric mean ratios of maximum blood concentration, area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, and area under the plasma concentration-time curve from time 0 to infinity for regorafenib were as follows: 94.7%, 91.4%, and 91.7%, respectively, under fasting conditions; and 94.6%, 97.7%, and 98.8%, respectively, under fed conditions. The 90% confidence intervals for the geometric mean ratios were within the 80%-125% equivalence interval for both the fasting and fed tests. Ingesting high-fat and high-calorie foods increases exposure to regorafenib, leading to slower rates of absorption. The safety profiles of the 2 preparations were similar.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1317-1323"},"PeriodicalIF":1.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496442","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 Bioequivalence Study of Azilsartan in Healthy Chinese Subjects 阿齐沙坦在中国健康受试者中的生物等效性研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-18 DOI: 10.1002/cpdd.1479

Xiaobei Liu, Xiangrong Dai, Xiaohui Yu, Huan Zhou, Jing Xie

{"title":"A Bioequivalence Study of Azilsartan in Healthy Chinese Subjects","authors":"Xiaobei Liu, Xiangrong Dai, Xiaohui Yu, Huan Zhou, Jing Xie","doi":"10.1002/cpdd.1479","DOIUrl":"10.1002/cpdd.1479","url":null,"abstract":"Azilsartan is an angiotensin II receptor blocker used for treating adult hypertension. It significantly improves cardiovascular outcomes in patients with high-risk hypertension, heart failure, and diabetic nephropathy. A single-center, randomized, open-label, single-dose, dual-cycle, dual-crossover clinical trial was conducted to evaluate the bioequivalence of azilsartan under fasting and postprandial conditions in 60 Chinese healthy volunteers. Thirty healthy subjects were enrolled in each test group, with random cross-administration for fasting and postprandial tests. The concentration of azilsartan in human plasma was evaluated using liquid chromatography-tandem mass spectrometry after a single oral administration of test and reference preparations, each at a dose of 20 mg (1 tablet). Pharmacokinetic parameters were determined using WinNonlin8.2 software, and bioequivalence was evaluated using SAS 9.4 software. The geometric mean ratios and 90% confidence intervals for maximum concentration, area under the plasma concentration-time curve from time 0 to the time of last measurable concentration, and area under the plasma concentration-time curve from time 0 to infinity of the test and reference preparations in the fasting and postprandial test groups were in the range of 80%-125%. The incidence of adverse events in the fasting and postprandial test groups was 30% (9/30) and 33.3% (10/30), respectively. No serious adverse events or unexpected adverse drug reactions were observed. In conclusion, the test and reference preparations of azilsartan tablets demonstrate bioequivalence and good safety in healthy Chinese subjects under fasting and postprandial conditions.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1301-1307"},"PeriodicalIF":1.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459790","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

Lack of Concentration-QTc Relationship and Cardiac Risk With Vatiquinone Therapeutic and Supratherapeutic Doses 瓦替喹酮治疗剂量和超治疗剂量缺乏浓度-QTc 关系和心脏病风险。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-17 DOI: 10.1002/cpdd.1476

Lucy Lee, Stephen Flach, Hongqi Xue, Lavanya Arivelu, Lee Golden, Ronald Kong, Borje Darpo

{"title":"Lack of Concentration-QTc Relationship and Cardiac Risk With Vatiquinone Therapeutic and Supratherapeutic Doses","authors":"Lucy Lee, Stephen Flach, Hongqi Xue, Lavanya Arivelu, Lee Golden, Ronald Kong, Borje Darpo","doi":"10.1002/cpdd.1476","DOIUrl":"10.1002/cpdd.1476","url":null,"abstract":"Vatiquinone, a 15-lipoxygenase inhibitor, is in development for patients with Friedreich ataxia. The study determined the effect of vatiquinone on electrocardiogram parameters. This was a 2-part, single-center, randomized, double-blinded, and placebo-controlled study. Part 1 used an adaptive approach to identify a supratherapeutic dose, while Part 2 evaluated the effect of vatiquinone on Fridericia corrected QT interval (QTcF). A safe and tolerated supratherapeutic dose of 1400 mg was identified. Concentration-QTcF analysis confirmed there was no statistically significant relationship between vatiquinone concentration and QTcF. QTcF effect (ie, ΔΔQTcF) exceeding 10 milliseconds was excluded for concentrations up to approximately 11,500 ng/mL. By-time-point analysis confirmed that least-squares mean ΔΔQTcF was below 10 milliseconds. Largest least-squares mean ΔΔQTcF of 1.5 milliseconds was observed at 2 hours after dosing. Vatiquinone did not have a clinically relevant effect on heart rate nor on cardiac conduction (PR interval and QRS interval). No new safety signals were found, as safety data are consistent with the known safety profile of vatiquinone. These findings altogether demonstrated that there is a minimal cardiac risk for vatiquinone concentrations up to the supratherapeutic dose level.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1227-1238"},"PeriodicalIF":1.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459792","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 Analysis of Clindamycin Hydrochloride Capsules in Healthy Chinese Subjects Under Fasted and Fed Conditions. 空腹和进食条件下中国健康受试者服用盐酸克林霉素胶囊的生物等效性分析

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-17 DOI: 10.1002/cpdd.1480

Zhi Wang, Haitang Wen, Xuebing Qian, Min Huang, Guohua Cheng, Guoping Zhong

{"title":"Bioequivalence Analysis of Clindamycin Hydrochloride Capsules in Healthy Chinese Subjects Under Fasted and Fed Conditions.","authors":"Zhi Wang, Haitang Wen, Xuebing Qian, Min Huang, Guohua Cheng, Guoping Zhong","doi":"10.1002/cpdd.1480","DOIUrl":"https://doi.org/10.1002/cpdd.1480","url":null,"abstract":"Clindamycin is a lincosamide antibiotic for the treatment of staphylococcal, streptococcal, and anaerobic bacterial infections. We conducted a single-center, single-dose, 2-preparation, 2-period, 2-sequence, randomized, open-label, 2 × 2 crossover study to evaluate the pharmacokinetics (PKs) and safety of the test and reference clindamycin hydrochloride capsules in healthy Chinese subjects under both fasted and fed conditions. Forty-eight subjects were enrolled in the study totally, with 24 subjects in each group. All subjects were asked to take a test or reference preparation, under either fasted or fed condition, and their blood samples were collected and assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. PK parameters including maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the last concentration, and area under the plasma concentration-time curve from time 0 to infinity were estimated with noncompartmental model and analyzed. Results showed that the PK profiles of the 2 preparations were consistent and met the bioequivalence criteria. Food was identified as a factor that had an impact on clindamycin absorption. The safety of clindamycin hydrochloride capsules was satisfactory. This study proved that the 2 clindamycin hydrochloride capsules were bioequivalent in healthy Chinese subjects under both fasted and fed conditions.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459791","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, Pharmacodynamics, and Pharmacokinetics of Recombinant Neorudin, a New Anticoagulant Drug in Patients With Acute Coronary Syndrome 急性冠状动脉综合征患者服用新型抗凝药物重组 Neorudin 的安全性、耐受性、药效学和药代动力学。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-09 DOI: 10.1002/cpdd.1478

Yu-bin Liu, Yan Liang, Hui-chen Liu, Guang-xun Feng, Xing-chen Zhou, Lin Zhang, Xiao-long Zhang, Qiang Li, Bo-yuan Ren, Xia Xia, Jun Zhu, Chu-tse Wu, Ji-de Jin

{"title":"Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Recombinant Neorudin, a New Anticoagulant Drug in Patients With Acute Coronary Syndrome","authors":"Yu-bin Liu, Yan Liang, Hui-chen Liu, Guang-xun Feng, Xing-chen Zhou, Lin Zhang, Xiao-long Zhang, Qiang Li, Bo-yuan Ren, Xia Xia, Jun Zhu, Chu-tse Wu, Ji-de Jin","doi":"10.1002/cpdd.1478","DOIUrl":"10.1002/cpdd.1478","url":null,"abstract":"This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR-hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open-label, single-center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low-, medium-, and high-dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half-life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3-day period.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1189-1197"},"PeriodicalIF":1.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388640","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