Clinical Pharmacology in Drug Development最新文献_第6页

Pharmacokinetic and Bioequivalence Evaluation of Dihydroxyaluminum Aminoacetate, Heavy Magnesium Carbonate, and Aspirin Tablets in Healthy Chinese Subjects in the Fasting and Postprandial Conditions 健康中国受试者在空腹和餐后状态下服用二羟基氨基乙酸铝、重质碳酸镁和阿司匹林片剂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 : 2024-07-31 DOI: 10.1002/cpdd.1455

Fang Yao, Yingxia He, Pan Lu, Jie Wang, Yafang Xie, Xiuwen Li, Qiangwei Liu, Yang Liu, Dan Cao, Jun Liang, Guan Liu

{"title":"Pharmacokinetic and Bioequivalence Evaluation of Dihydroxyaluminum Aminoacetate, Heavy Magnesium Carbonate, and Aspirin Tablets in Healthy Chinese Subjects in the Fasting and Postprandial Conditions","authors":"Fang Yao, Yingxia He, Pan Lu, Jie Wang, Yafang Xie, Xiuwen Li, Qiangwei Liu, Yang Liu, Dan Cao, Jun Liang, Guan Liu","doi":"10.1002/cpdd.1455","DOIUrl":"10.1002/cpdd.1455","url":null,"abstract":"Dihydroxyaluminum aminoacetate, heavy magnesium carbonate, and aspirin tablets is a new combined aspirin preparation, each containing aspirin (81 mg), dihydroxyaluminum aminoacetate (11 mg), and heavy magnesium carbonate (22 mg). This study was conducted to evaluate the pharmacokinetic (PK) and bioequivalence in healthy Chinese subjects. This randomized, open-label, single-dose, 2-sequence, and 2-period crossover study included 78 healthy volunteers (fasting, n = 36; postprandial, n = 42). Blood samples were collected for PK analysis. Aspirin and salicylic acid concentrations in human plasma were determined by liquid chromatography-tandem mass spectrometry. Safety and tolerability were monitored. There were no significant differences between the test and reference formulations in maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, or AUC from time 0 to infinity. The 90% confidence intervals of the test and reference formulations of maximum plasma concentration, AUC from time 0 to time t, and AUC from time 0 to infinity were within the acceptable range (80%-125%) under fasting and postprandial conditions. All adverse events were mild and no serious adverse events were observed in the study. Both compounds were well tolerated in healthy Chinese volunteers.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1157-1163"},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Implications of Co-administering Apixaban with Key Interacting Medications 阿哌沙班与主要相互作用药物联合用药的临床意义。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-24 DOI: 10.1002/cpdd.1446

Nicholas Favatella, David Dalton, Wonkyung Byon, Samira J. Merali, Christian Klem

引用次数: 0

Effect of Erdafitinib on the Pharmacokinetics of Midazolam and Metformin in Patients With Advanced Solid Tumors Harboring FGFR Gene Alterations 厄达非替尼对携带表皮生长因子受体基因改变的晚期实体瘤患者服用咪达唑仑和二甲双胍药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-24 DOI: 10.1002/cpdd.1445

Wei Zhu, Mahadi Baig, Vahid Naini, Marc De Meulder, Sydney Akapame, Loeckie De Zwart, Nahor Haddish-Berhane, Spyros Triantos

{"title":"Effect of Erdafitinib on the Pharmacokinetics of Midazolam and Metformin in Patients With Advanced Solid Tumors Harboring FGFR Gene Alterations","authors":"Wei Zhu, Mahadi Baig, Vahid Naini, Marc De Meulder, Sydney Akapame, Loeckie De Zwart, Nahor Haddish-Berhane, Spyros Triantos","doi":"10.1002/cpdd.1445","DOIUrl":"10.1002/cpdd.1445","url":null,"abstract":"Erdafitinib, an oral pan-FGFR inhibitor, is used in locally advanced or metastatic urothelial carcinoma for adults with FGFR3 genetic alterations and whose disease progressed following prior systemic therapy. This drug-drug interaction substudy evaluated the effect of erdafitinib on the pharmacokinetics of midazolam (cytochrome P450 3A4 substrate), and metformin (organic cation transporter 2 substrate). Twenty-five patients with advanced solid tumors harboring FGFR gene alterations received pretreatment with single doses of midazolam and metformin, followed by a daily dose of erdafitinib. Drug-drug interaction assessments were performed at erdafitinib steady state following coadministration of single doses of midazolam and metformin, respectively. Geometric mean ratios for maximum plasma concentration and area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity were estimated using linear mixed-effects models (90% confidence interval within 80%-125% indicated no interaction). The 90% confidence intervals of geometric mean ratios for maximum plasma concentration, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity of midazolam (86.3%, 88.5%, and 82.1%), 1-OH midazolam (99.8%, 97.4%, and 101.5%), and metformin (108.7%, 119.0%, and 113.9%) were either contained or slightly outside the 80%-125% interval and not considered clinically meaningful. Adverse events were consistent with the known erdafitinib safety profile; no new safety signals emerged. Thus, repeated dosing of erdafitinib had no clinically meaningful effect on the pharmacokinetics of midazolam or metformin.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1164-1176"},"PeriodicalIF":1.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751314","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

Pharmacokinetic Profile and Comparative Bioavailability of an Oral Fixed-Dose Combination of Metformin and Acetylsalicylic Acid (Aspirin) 二甲双胍和乙酰水杨酸（阿司匹林）口服固定剂量复方制剂的药代动力学特征和生物利用度比较。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-22 DOI: 10.1002/cpdd.1450

Lourdes Garza-Ocañas, Christian T. Badillo-Castañeda, Sandra L. Montoya-Eguía, Maria T. Zanatta-Calderón, Pedro Lennon Sáenz-Chávez, Julia D. Torres-Garza, Ileana C. Rodriguez-Vazquez, Yulia Romero-Antonio, Kevin F. Rios-Brito, Jorge González-Canudas

{"title":"Pharmacokinetic Profile and Comparative Bioavailability of an Oral Fixed-Dose Combination of Metformin and Acetylsalicylic Acid (Aspirin)","authors":"Lourdes Garza-Ocañas, Christian T. Badillo-Castañeda, Sandra L. Montoya-Eguía, Maria T. Zanatta-Calderón, Pedro Lennon Sáenz-Chávez, Julia D. Torres-Garza, Ileana C. Rodriguez-Vazquez, Yulia Romero-Antonio, Kevin F. Rios-Brito, Jorge González-Canudas","doi":"10.1002/cpdd.1450","DOIUrl":"10.1002/cpdd.1450","url":null,"abstract":"Patients with diabetes face a 2-4-fold greater cardiovascular risk compared to those without diabetes. Both metformin and acetylsalicylic acid (aspirin) treatment have demonstrated a significant reduction in this risk. This single-center, open-label, sequence randomized, 2 × 2 crossover, single-dose clinical trial evaluated the pharmacokinetics profile and comparative bioavailability of a novel oral fixed-dose combination (FDC) of metformin/acetylsalicylic acid (500/100 mg tablet) versus the reference mono-drugs administered concomitantly, metformin 500 mg tablet and acetylsalicylic acid 100 mg tablet, in 22 healthy Mexican adult volunteers under fasting conditions. Blood samples were collected predose and at specified intervals across a 24-hour period following administration and were analyzed for metformin and salicylic acid using high-performance liquid chromatography coupled with tandem mass spectrometry. Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0-t), and (area under the plasma drug concentration-time cruve from 0 up to infinity (AUC0∞) data were within the range of 80%-125%. The results obtained from the present clinical study demonstrate the comparative bioavailability of the FDC when compared with the coadministration of reference mono-drugs. There were no adverse events or adverse reactions reported throughout the study.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1245-1252"},"PeriodicalIF":1.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733719","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 Bioequivalence of Abexinostat (CRA-024781) Tosylate Tablets (20 mg) in Chinese Healthy Subjects Under Fasting Conditions 中国健康受试者在空腹条件下服用阿贝司他（CRA-024781）对甲苯磺酰苯胺片（20 毫克）的生物等效性研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-18 DOI: 10.1002/cpdd.1448

Xiang Li, Wenqiang Guo, Jian Chen, Gewen Tan

引用次数: 0

Impact of a High-Fat Meal on the Pharmacokinetics of Sotorasib, a KRAS G12C Inhibitor 高脂餐对 KRAS G12C 抑制剂 Sotorasib 药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-17 DOI: 10.1002/cpdd.1452

Panli Cardona, Sandeep Dutta, Brett Houk

{"title":"Impact of a High-Fat Meal on the Pharmacokinetics of Sotorasib, a KRAS G12C Inhibitor","authors":"Panli Cardona, Sandeep Dutta, Brett Houk","doi":"10.1002/cpdd.1452","DOIUrl":"10.1002/cpdd.1452","url":null,"abstract":"Sotorasib is a small molecule drug that specifically and irreversibly inhibits the KRAS p.G12C mutant protein. This analysis investigated the impact of a high-calorie high-fat meal on the pharmacokinetics, safety, and tolerability of sotorasib in both healthy volunteers and patients with KRAS G12C advanced solid tumors. Each subject received a single oral dose of 360 or 960 mg of sotorasib under fasted conditions or with a high-fat meal (fed conditions). The geometric least squares means (GLSM) ratios (fed/fasted) for 360 mg of sotorasib Cmax and AUCinf were 1.03 and 1.38, respectively, in healthy volunteers (N = 14). The GLSM ratios (fed/fasted) for Cmax and AUC0-24h were 1.38 and 1.75, respectively, with 360 mg of sotorasib in cancer patients (N = 2). The GLSM ratios (fed/fasted) for Cmax and AUC0-24h were 0.660 and 1.25, respectively, with 960 mg of sotorasib in cancer patients (N = 8). Sotorasib was well tolerated in fast and fed conditions. The impact of a high-fat meal on sotorasib exposure is less than a 2-fold increase or decrease in Cmax and AUCs.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1219-1226"},"PeriodicalIF":1.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626231","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 Food Effect Assessment of Eltrombopag Olamine Tablets in Healthy Chinese Subjects: An Open, Randomized, Single-Dose, and Two-Period Crossover Study 艾曲波帕格欧拉明片在中国健康受试者中的生物等效性和食物效应评估：一项开放、随机、单剂量和两期交叉研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-16 DOI: 10.1002/cpdd.1453

Jingyan Wang, Zhicheng Zhao, Ye Tao, Yi Lan

{"title":"Bioequivalence and Food Effect Assessment of Eltrombopag Olamine Tablets in Healthy Chinese Subjects: An Open, Randomized, Single-Dose, and Two-Period Crossover Study","authors":"Jingyan Wang, Zhicheng Zhao, Ye Tao, Yi Lan","doi":"10.1002/cpdd.1453","DOIUrl":"10.1002/cpdd.1453","url":null,"abstract":"Eltrombopag, a nonpeptide thrombopoietin receptor agonist, is primarily used for treating immune thrombocytopenic purpura. The aim of this study was to investigate the pharmacokinetic profile and food-drug interaction of test and reference eltrombopag olamine tablets among healthy Chinese volunteers. An open, randomized, single-dose, 2-period crossover design was employed, involving fasting and fed conditions with a 10-day washout period. Ninety-six healthy volunteers received a single oral dose of 25 mg of the 2 eltrombopag formulations, with 48 participants in each group: fasting volunteers and those consuming a high-fat, low-calcium meal. Plasma eltrombopag concentrations were analyzed using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were derived from the concentration-time profiles. The geometric mean ratios, with 90% confidence intervals, for the maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable concentration, and area under the concentration-time curve from time 0 to infinity fell within the bioequivalence acceptance criteria (80%-125%) under both fasting and fed conditions, indicating bioequivalence between the test and reference formulations. Administration of eltrombopag with a high-fat, low-calcium diet reduced the net systemic exposure by approximately 40%. Adverse events were recorded, and no serious adverse events were observed in either fasting or fed conditions. In conclusion, eltrombopag is well tolerated and exhibits a favorable safety profile in the Chinese population. The achievement of bioequivalence under fasting and fed conditions supports the demonstration of biosimilarity between the test and reference formulations.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1260-1266"},"PeriodicalIF":1.5,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Population Pharmacokinetics and Exposure-Response Relationship of Zimberelimab in Chinese Patients with Advanced Tumors 齐贝瑞单抗在中国晚期肿瘤患者中的群体药代动力学及暴露-反应关系

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-15 DOI: 10.1002/cpdd.1439

Fang Yang, Yongying Lu, Lihui Bai, Chenhui Deng, Zhen Liu, Zhihua Sun, Li Li, Shicong Wang, Li Zhou, Haifeng Feng, Shaoyu Yan, Jiman Zhu

{"title":"Population Pharmacokinetics and Exposure-Response Relationship of Zimberelimab in Chinese Patients with Advanced Tumors","authors":"Fang Yang, Yongying Lu, Lihui Bai, Chenhui Deng, Zhen Liu, Zhihua Sun, Li Li, Shicong Wang, Li Zhou, Haifeng Feng, Shaoyu Yan, Jiman Zhu","doi":"10.1002/cpdd.1439","DOIUrl":"10.1002/cpdd.1439","url":null,"abstract":"This study aimed to establish a population pharmacokinetic (PopPK) model using data from 2 clinical trials of zimberelimab, evaluate the pharmacokinetics (PKs) of zimberelimab, explore the feasibility of 360 mg once every 3 weeks (Q3W) and 480 mg once every 4 weeks (Q4W) as alternative dosage regimens, and analyze the exposure-response relationship of the efficacy and safety of zimberelimab for advanced tumors. The PKs of zimberelimab were described using the 2-compartment model with time-dependent nonlinear elimination. The prediction-corrected visual predictive check was used to evaluate the model's predictive value on blood drug concentrations. In total, 2165 PK observations from 321 participants were included. The PopPK model demonstrated a high level of concordance between the observed data and the predicted values, indicative of a robust fit to the PK data of zimberelimab. The PK variables were similar for the 240 mg once every 2 weeks, 360 mg Q3W, and 480 mg Q4W regimens. No covariates significantly affecting the PK variables in the final model were found. The exposure variables of zimberelimab have no obvious correlations with efficacy and safety, and 360 mg Q3W and 480 mg Q4W are worthy of further study. This study establishes a PopPK model and analyzes the exposure-response relationship of zimberelimab, which helps to explore the potential for alternative dosing regimens and offers a foundation for optimizing therapeutic strategies for advanced cancer patients through simulation-based methods.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 8","pages":"897-906"},"PeriodicalIF":1.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619509","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 a High-Fat Meal on the Pharmacokinetics of an Immediate Release Atogepant Tablet 高脂餐对阿托吉潘缓释片药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-12 DOI: 10.1002/cpdd.1451

Ramesh R. Boinpally, Joel M. Trugman

{"title":"Effect of a High-Fat Meal on the Pharmacokinetics of an Immediate Release Atogepant Tablet","authors":"Ramesh R. Boinpally, Joel M. Trugman","doi":"10.1002/cpdd.1451","DOIUrl":"10.1002/cpdd.1451","url":null,"abstract":"Atogepant, an oral calcitonin gene-related peptide receptor antagonist, is approved for the preventive treatment of migraine. A phase 1, open-label, single-dose, 2-period crossover study evaluated the effect of a high-fat meal on the pharmacokinetics and safety of atogepant in 20 healthy adults. Administration of atogepant 60 mg immediate-release (IR) tablets under fed conditions reduced the area under the plasma concentration-time curve (AUC) from 0 to time t and from 0 to time infinity by approximately 18% and reduced the maximum plasma concentration (Cmax) by 22%. The 90% confidence intervals for the geometric mean ratios of Cmax and AUC were not contained within the bioequivalence limits of 80%-125%. There was no change in the median time to maximum plasma concentration in the fed versus fasted state. The incidence of treatment-emergent adverse events (TEAEs) was similar between fed and fasted conditions. Four TEAEs were considered related to study intervention and were reported after participants received atogepant under fasted conditions (3 participants). A single-dose atogepant 60 mg IR tablet was safe and tolerated under both fed and fasted states. Due to the wide effective dose range of 10-60 mg/day for atogepant for the preventive treatment of migraine, the food effect on its pharmacokinetics is not considered clinically relevant.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1212-1218"},"PeriodicalIF":1.5,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589827","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

Effect of Mild or Moderate Hepatic Impairment on the Pharmacokinetics of Avacopan, a Small-Molecule Complement C5a Receptor Antagonist, for the Treatment of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis 轻度或中度肝功能损害对用于治疗抗中性粒细胞胞浆自身抗体相关性血管炎的小分子补体 C5a 受体拮抗剂 Avacopan 的药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-11 DOI: 10.1002/cpdd.1444

Shichang Miao, Pablo Suso, John A. Furst, Matthew G. Hudson, Ashit Trivedi

{"title":"Effect of Mild or Moderate Hepatic Impairment on the Pharmacokinetics of Avacopan, a Small-Molecule Complement C5a Receptor Antagonist, for the Treatment of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis","authors":"Shichang Miao, Pablo Suso, John A. Furst, Matthew G. Hudson, Ashit Trivedi","doi":"10.1002/cpdd.1444","DOIUrl":"10.1002/cpdd.1444","url":null,"abstract":"Avacopan is currently approved in several regions of the world as an oral treatment in combination with standard therapy, including glucocorticoids, for adult patients with severe active antineutrophil cytoplasmic autoantibody-associated vasculitis. In vitro and clinical studies have established that avacopan is primarily eliminated through cytochrome P450 3A4 metabolism. This Phase 1, open-label, single-dose study (ClinicalTrials.gov identifier: NCT06004934) was conducted to evaluate the effect of mild (n = 8) or moderate (n = 8) hepatic impairment compared with normal hepatic function (n = 8) on the pharmacokinetics, safety, and tolerability of a single oral dose of 30 mg of avacopan in patients without active antineutrophil cytoplasmic autoantibody-associated vasculitis. Relative to participants with normal hepatic function, in participants with mild or moderate hepatic impairment, the avacopan area under the plasma concentration-time curve from time 0 to infinity geometric mean ratios (90% confidence intervals) were 1.3 (0.9-2.0) and 1.1 (0.6-2.0), respectively, and the avacopan maximum plasma concentration geometric mean ratios (90% CIs) were 1.0 (0.8-1.3) and 0.8 (0.6-1.1), respectively. The geometric mean ratios of metabolite M1 also revealed no pharmacokinetically relevant increase in the peak exposure of M1 in participants with mild or moderate hepatic impairment. Thus, no avacopan dosage adjustment is necessary for patients with mild or moderate hepatic impairment.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"1000-1010"},"PeriodicalIF":1.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589828","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