Clinical Pharmacology in Drug Development最新文献_第10页

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":"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":"14 2","pages":"154-160"},"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":"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":"14 2","pages":"127-132"},"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

Population Pharmacokinetics Modeling and Simulation of Deutenzalutamide, A Novel Androgen Receptor Antagonist, in Patients With Metastatic Castration-Resistant Prostate Cancer 新型雄激素受体拮抗剂 Deutenzalutamide 在转移性抗性前列腺癌患者中的群体药代动力学建模与模拟。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-10-04 DOI: 10.1002/cpdd.1477

Yixian Liu, Yongji He, Xiaohui Qi, Xinghai Li, Yi Zhou, Yuanwei Chen, Zhenlei Wang, Li Zheng

{"title":"Population Pharmacokinetics Modeling and Simulation of Deutenzalutamide, A Novel Androgen Receptor Antagonist, in Patients With Metastatic Castration-Resistant Prostate Cancer","authors":"Yixian Liu, Yongji He, Xiaohui Qi, Xinghai Li, Yi Zhou, Yuanwei Chen, Zhenlei Wang, Li Zheng","doi":"10.1002/cpdd.1477","DOIUrl":"10.1002/cpdd.1477","url":null,"abstract":"Deutenzalutamide is a new molecular entity androgen receptor antagonist. The primary aim of this study was to develop a population pharmacokinetic model of deutenzalutamide and evaluate effects of intrinsic and extrinsic factors on pharmacokinetics. A nonlinear mixed-effects modeling approach was performed to develop the population pharmacokinetic of deutenzalutamide using data from 1 Phase I trial of deutenzalutamide. Goodness-of-fit plots, prediction-corrected visual predictive check, and bootstrap analysis were carried out to evaluate the final model. Simulation for the developed model was used to evaluate the covariate effects on the pharmacokinetics of deutenzalutamide. A 2-compartment model with first-order absorption and elimination from the central compartment was established for deutenzalutamide. The final covariate included body weight on peripheral compartment volume. This is the first research developing the population pharmacokinetic model of deutenzalutamide in patients with metastatic castration-resistant prostate cancer, and it is expected to support the future clinical administration of deutenzalutamide.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1291-1300"},"PeriodicalIF":1.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phase 1 Evaluation of the Bioequivalence and Drug-Drug Interaction Potential of a Novel Fixed-Dose Combination of Ezetimibe, Atorvastatin, and Amlodipine 对依折麦布、阿托伐他汀和氨氯地平的新型固定剂量复方制剂的生物等效性和药物相互作用潜力的第一阶段评估

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-27 DOI: 10.1002/cpdd.1472

Hyung Soon Lim, Jae Hoon Kim, Jang Hee Hong, Jin-Gyu Jung, Jung Sunwoo

{"title":"Phase 1 Evaluation of the Bioequivalence and Drug-Drug Interaction Potential of a Novel Fixed-Dose Combination of Ezetimibe, Atorvastatin, and Amlodipine","authors":"Hyung Soon Lim, Jae Hoon Kim, Jang Hee Hong, Jin-Gyu Jung, Jung Sunwoo","doi":"10.1002/cpdd.1472","DOIUrl":"10.1002/cpdd.1472","url":null,"abstract":"A fixed-dose combination (FDC) of ezetimibe, atorvastatin, and amlodipine has been developed to improve medication adherence among patients with cardiovascular diseases. In a randomized, open-label, multiple-dose, fixed-sequence study involving 34 participants (Study 1), the potential drug-drug interaction between ezetimibe/atorvastatin FDC and amlodipine was evaluated. Additionally, a randomized, open-label, crossover study with 60 participants (Study 2) compared the pharmacokinetics (PKs) of ezetimibe/atorvastatin/amlodipine FDC to those of individual formulations. Co-administration of the ezetimibe/atorvastatin FDC and amlodipine did not significantly alter the PKs of either drug. However, amlodipine resulted in a slight increase in systemic exposure to atorvastatin by approximately 23%. Geometric mean ratios (FDC to individual formulations) and 90% confidence intervals of area under the time-concentration curve at steady state during dosing interval (AUCτ, ss) and maximum concentration at steady state (Cmax, ss) or amlodipine, atorvastatin, and ezetimibe were all within the bioequivalent range (0.8-1.25), confirming bioequivalence. Moreover, the FDC of ezetimibe, atorvastatin, and amlodipine exhibited comparable tolerability to corresponding individual formulations.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1345-1354"},"PeriodicalIF":1.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343021","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

Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Pritelivir and Its Metabolites 肾功能和肝功能受损对普利特韦及其代谢物药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-09-25 DOI: 10.1002/cpdd.1469

Katharina Erb-Zohar, Susanne Bonsmann, Jörg Pausch, Melanie Sumner, Alexander Birkmann, Holger Zimmermann, Atef Halabi, Dirk Kropeit

{"title":"Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Pritelivir and Its Metabolites","authors":"Katharina Erb-Zohar, Susanne Bonsmann, Jörg Pausch, Melanie Sumner, Alexander Birkmann, Holger Zimmermann, Atef Halabi, Dirk Kropeit","doi":"10.1002/cpdd.1469","DOIUrl":"10.1002/cpdd.1469","url":null,"abstract":"Two trials were performed to evaluate the effect of renal and hepatic impairment on the pharmacokinetics of pritelivir and its metabolites. The renal impairment trial included subjects with mild, moderate, and severe impairment, while the hepatic impairment trial included subjects with moderate impairment. Both trials recruited a matched control group of healthy subjects. Following a single oral dose of 100 mg of pritelivir, mild and moderate renal impairment and moderate hepatic impairment did not have a clinically relevant effect on the pharmacokinetics of pritelivir. In subjects with severe renal impairment, pritelivir exposure (area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) was 57% higher compared with controls. Pritelivir plasma protein binding was similar in subjects and controls with renal impairment, while the free fraction was higher in subjects with moderate hepatic impairment, increasing unbound pritelivir exposure by 23%. For the metabolites pyridinyl phenyl acetic acid (PPA), amino thiazole sulfonamide (ATS), and PPA-acyl glucuronide, generally higher exposure was observed with increasing degree of renal impairment (ie, moderate to severe), but not with mild impairment. A modest effect of moderate hepatic impairment was observed for PPA and ATS. Pritelivir was safe and well tolerated in healthy subjects and subjects with renal or hepatic impairment.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1198-1211"},"PeriodicalIF":1.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343020","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