Clinical Pharmacology in Drug Development最新文献

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2024 CPDD Abstract Booklet 2024 年美国临床药理学学院年会®。
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-09-01 DOI: 10.1002/cpdd.1459
{"title":"2024 CPDD Abstract Booklet","authors":"","doi":"10.1002/cpdd.1459","DOIUrl":"10.1002/cpdd.1459","url":null,"abstract":"<p><b>DATE: 9/8/2024</b></p><p><b>TIME: 5:00 PM – 7:00 PM</b></p><p><b>DATE: 9/9/2024</b></p><p><b>TIME: 5:00 PM – 7:00 PM</b></p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 S1","pages":"1-168"},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105084","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
Meta-Analysis of Noncompartmental Pharmacokinetic Parameters to Evaluate the Impact of CYP2C19 and CYP2C9 Genetic Polymorphisms on Abrocitinib Exposure 评估CYP2C19和CYP2C9基因多态性对阿罗西替尼暴露影响的非室间药代动力学参数的Meta分析。
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-08-30 DOI: 10.1002/cpdd.1465
Luke Fostvedt, Jian Liu, Xiaoxing Wang, Yinhua Li, Jillian Johnson, Linda Wood, Martin Dowty, Bimal Malhotra, Hernan Valdez, Timothy Nicholas, Wei Xue
{"title":"Meta-Analysis of Noncompartmental Pharmacokinetic Parameters to Evaluate the Impact of CYP2C19 and CYP2C9 Genetic Polymorphisms on Abrocitinib Exposure","authors":"Luke Fostvedt,&nbsp;Jian Liu,&nbsp;Xiaoxing Wang,&nbsp;Yinhua Li,&nbsp;Jillian Johnson,&nbsp;Linda Wood,&nbsp;Martin Dowty,&nbsp;Bimal Malhotra,&nbsp;Hernan Valdez,&nbsp;Timothy Nicholas,&nbsp;Wei Xue","doi":"10.1002/cpdd.1465","DOIUrl":"10.1002/cpdd.1465","url":null,"abstract":"<p>Abrocitinib is a selective Janus kinase 1 inhibitor approved for the treatment of atopic dermatitis. It is metabolized primarily by cytochrome P450 (CYP) 2C19 (approximately 53%) and CYP2C9 (approximately 30%), which form 2 active metabolites. The pharmacologic activity of abrocitinib is attributable to the unbound exposures of abrocitinib and those metabolites with active moiety area under the plasma concentration–time curve (AUC) considered the best measure of the total pharmacological effect. The effect of CYP2C19 and/or CYP2C9 genotypes on abrocitinib and active moiety exposures were evaluated using a meta-analysis of the noncompartmental estimates of exposure pooled from 10 clinical studies. A linear mixed-effects model was developed on the basis of the power model to evaluate the effect of CYP2C19 and/or CYP2C9 genotypes on exposure (i.e., abrocitinib AUC and peak plasma concentration, active moiety AUC and peak plasma concentration). The genotypes were evaluated individually and as a combined phenotype effect. When evaluating the poor metabolizers of CYP2C19 or CYP2C9 individually, the estimated increases were 44.9% and 42.0% in active moiety AUC, respectively. The combined phenotype models showed a 0.6% decrease, and 25.1% and 10.5% increases in the active moiety AUC for “elevated,” “mixed,” and “reduced” metabolizers, respectively. Overall, the active moiety exposures did not appear to be affected to a clinically meaningful extent by different genotypes of CYP2C19 and/or CYP2C9.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1098-1107"},"PeriodicalIF":1.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105083","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
Consideration of the Root Causes in Candidate Attrition During Oncology Drug Development 考虑肿瘤药物开发过程中候选药物流失的根本原因。
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-08-20 DOI: 10.1002/cpdd.1464
Yin-Ming Kuo, Jeffrey S. Barrett
{"title":"Consideration of the Root Causes in Candidate Attrition During Oncology Drug Development","authors":"Yin-Ming Kuo,&nbsp;Jeffrey S. Barrett","doi":"10.1002/cpdd.1464","DOIUrl":"10.1002/cpdd.1464","url":null,"abstract":"&lt;p&gt;Cancer remained the second-leading cause of death in the United States in 2020, based on the data from the US Centers for Disease Control and Prevention. While there have been lots of money and time devoted to this therapeutic area, the needs from these patients with cancer were still substantial. The fundamental issue is high attrition rate for oncology drugs, which contributes to the higher cost for oncology drug developers. The study for the success rate from first-in-human trials to registration for 10 big pharmaceutical companies in the United States and Europe indicated that the average success rate in all therapeutic fields was about 11% from 1991 to 2000.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The success rates varied between different therapeutic areas, whereas oncology drugs had a relatively low success rate, approximately 5%. In other words, only 1 in 20 new chemical entities passed through clinical trials and received an approval from the European and/or the US regulatory authorities. Kola and Landis also studied the reasons for drug attrition during drug development from 1991 to 2000. They discovered that the primary reason for drug attrition changed from inappropriate pharmacokinetics (PK) and low bioavailability (approximately 40%) in 1991 to a lack of efficacy and safety (approximately 60%) in 2000.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Kola and Landis concluded 2 strategies that may reduce the rate of attrition. First, in some therapeutic areas with lower success rates (eg, oncology and central nervous system), appropriate animal models and biomarkers have to be carefully chosen during early drug discovery and development stages.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; For example, a transgenic animal model is more suitable than a xenograft animal model for preclinical studies of oncology drugs. Second, Kola and Landis observed that biologics had a higher success rate to launch from the first-in-human studies, especially in the areas of immunology and cancer, implying that biologics are safer than conventional chemical drugs.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Antibody drugs, 1 group of biologics, generally have fewer safety concerns and fewer PK issues.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; In general, antibodies possess a few pharmacological characteristics, including high potency, limited off-target toxicity, and a low risk of biotransformation to toxic metabolites.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Thus, the possibility of drug-drug interactions or renal and hepatic impairment on drug excretion is relatively low, which could significantly eliminate a few matters that could potentially result in drug attrition.&lt;/p&gt;&lt;p&gt;On the other hand, Walker and Newell analyzed the data for small molecular cancer drugs on the attrition from 1995 to 2007, indicating that the attrition rate within the oncology field was 82%; however, the attrition rate of kinase inhibitors was 53%.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; It is worth noticing that kinase inhibitors were more successful in the high-risk transition from Ph","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"952-960"},"PeriodicalIF":1.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003787","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 Safety of Linezolid Tablets of 2 Different Manufacturers in Healthy Chinese Subjects in Fasting and Fed States 中国健康受试者在空腹和进食状态下服用两种不同厂家生产的利奈唑胺片剂的药代动力学和安全性
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-08-19 DOI: 10.1002/cpdd.1462
Hanjing Chen, Hongrong Xu, Fei Yuan, Hui Li, Lei Sheng, Chao Liu, Weili Chen, Xuening Li
{"title":"Pharmacokinetics and Safety of Linezolid Tablets of 2 Different Manufacturers in Healthy Chinese Subjects in Fasting and Fed States","authors":"Hanjing Chen,&nbsp;Hongrong Xu,&nbsp;Fei Yuan,&nbsp;Hui Li,&nbsp;Lei Sheng,&nbsp;Chao Liu,&nbsp;Weili Chen,&nbsp;Xuening Li","doi":"10.1002/cpdd.1462","DOIUrl":"10.1002/cpdd.1462","url":null,"abstract":"<p>This study aimed to evaluate the pharmacokinetics (PKs) and safety of a generic drug, linezolid, compared to those of a reference drug in healthy Chinese subjects under both fasting and fed conditions. This was a randomized, open-label, 2-period, 2-sequence crossover study. The subjects received a single dose of the test or reference drug, linezolid (600 mg), in each period. The PK parameters were calculated using a non-compartmental method and compared between the 2 drugs. Bioequivalence was analyzed using geometric mean ratios (GMRs) of the 2 formulations and their corresponding 90% confidence intervals (CIs). The safety of the 2 formulations was assessed under both fasting and fed conditions. Forty-eight subjects completed the study, 24 each in the fasting and feeding groups. The average plasma concentration-time patterns of linezolid were similar for both medications under both conditions. The GMR and 90% CIs of the maximum plasma concentration and the area under the plasma concentration-time curve of linezolid were ranged from 0.80 to 1.25. Both drugs were well tolerated with a similar incidence of adverse drug reactions. In conclusion, the PK and safety profiles of the 2 formulations were comparable. Food intake did not influence the PK profiles of linezolid. These results suggest that the test drug can be used as an alternative to reference drugs.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1239-1244"},"PeriodicalIF":1.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999546","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 Safety of Generic Glecaprevir/Pibrentasvir Compared to a Branded Product: A Randomized, Crossover Study in Healthy Volunteers 与品牌产品相比,仿制药 Glecaprevir/Pibrentasvir 的生物等效性和安全性:一项针对健康志愿者的随机交叉研究。
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-08-14 DOI: 10.1002/cpdd.1463
Sergei Noskov, Olesya Parulya, Lyudmila Lutskova, Anna Arefeva, Ekaterina Protsenko, Veniamin Banko, Kseniia Radaeva, Iuliia Matvienko, Maria Gefen, Polina Karnakova, Alina Knyazeva, Timofey Komarov, Olga Archakova, Igor Shohin
{"title":"Bioequivalence and Safety of Generic Glecaprevir/Pibrentasvir Compared to a Branded Product: A Randomized, Crossover Study in Healthy Volunteers","authors":"Sergei Noskov,&nbsp;Olesya Parulya,&nbsp;Lyudmila Lutskova,&nbsp;Anna Arefeva,&nbsp;Ekaterina Protsenko,&nbsp;Veniamin Banko,&nbsp;Kseniia Radaeva,&nbsp;Iuliia Matvienko,&nbsp;Maria Gefen,&nbsp;Polina Karnakova,&nbsp;Alina Knyazeva,&nbsp;Timofey Komarov,&nbsp;Olga Archakova,&nbsp;Igor Shohin","doi":"10.1002/cpdd.1463","DOIUrl":"10.1002/cpdd.1463","url":null,"abstract":"<p>This was an open-label, randomized, single-dose, 2-period, crossover clinical trial with an adaptive design to evaluate the bioequivalence and comparative pharmacokinetics of generic glecaprevir/pibrentasvir versus the brand name product in healthy White male and female volunteers under fed conditions. Safety profiles were also assessed. A total of 56 healthy adult volunteers were enrolled and randomly assigned in a 1:1 ratio to receive a single dose of either the generic or reference formulation. After a 7-day washout period, subjects received the alternate product. Blood samples were collected at pre-specified time points up to 48 hours post-dosing. Plasma concentrations of glecaprevir and pibrentasvir were determined using a validated high-performance liquid chromatography-tandem mass spectrometry method. The geometric mean ratios of the test to the reference formulation for maximum plasma concentration (C<sub>max</sub>) and area under the concentration-time curve from drug administration to the last measurable concentration (AUC<sub>0-t</sub>) fell within the predefined bioequivalence range of 80%-125%. Both formulations demonstrated comparable pharmacokinetic profiles for glecaprevir and pibrentasvir, and can be considered bioequivalent. No adverse events were reported, and both formulations were well tolerated by all participants.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1331-1338"},"PeriodicalIF":1.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975282","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 Itraconazole, a CYP3A4 Inhibitor, and Rifampin, a CYP3A4 Inducer, on the Pharmacokinetics of Vatiquinone CYP3A4抑制剂伊曲康唑和CYP3A4诱导剂利福平对瓦替喹酮药代动力学的影响
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-08-12 DOI: 10.1002/cpdd.1461
Lucy Lee, Martin Thoolen, Jiyuan Ma, Diksha Kaushik, Lee Golden, Ronald Kong
{"title":"Effect of Itraconazole, a CYP3A4 Inhibitor, and Rifampin, a CYP3A4 Inducer, on the Pharmacokinetics of Vatiquinone","authors":"Lucy Lee,&nbsp;Martin Thoolen,&nbsp;Jiyuan Ma,&nbsp;Diksha Kaushik,&nbsp;Lee Golden,&nbsp;Ronald Kong","doi":"10.1002/cpdd.1461","DOIUrl":"10.1002/cpdd.1461","url":null,"abstract":"<p>Vatiquinone is a small molecule inhibitor of 15-lipoxygenase in development for patients with Friedreich's ataxia. The objective of this analysis was to determine the effect of a cytochrome P450 isoform 3A4 (CYP3A4) inhibitor and inducer on vatiquinone pharmacokinetics (PKs). The coadministration of 400 mg of vatiquinone with 200 mg of itraconazole (a CYP3A4 inhibitor) resulted in increased maximum observed concentration (C<sub>max</sub>) of vatiquinone and systemic exposure (AUC<sub>0-inf</sub>) by approximately 3.5- and 2.9-fold, respectively. The coadministration of 400 mg of vatiquinone with 600 mg of rifampin (a CYP3A4 inducer) resulted in decreased vatiquinone C<sub>max</sub> and AUC<sub>0-inf</sub> by approximately 0.64- and 0.54-fold, respectively. The terminal half-life of vatiquinone was not affected by itraconazole or rifampin. These clinical study results confirm the in vitro reaction phenotyping data that shows that CYP3A4 plays an important role in vatiquinone metabolism. The result of this analysis together with phase 3 efficacy and safety data, population PK analysis, and the exposure-response relationship will determine if the extent of vatiquinone changes in the presence of CYP3A4 inhibitors and inducers are considered clinically relevant.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 12","pages":"1283-1290"},"PeriodicalIF":1.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916234","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
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Muscarinic M3 Receptor-Positive Allosteric Modulator ASP8302 Following Single and Multiple Ascending Oral Doses in Healthy Volunteers 在健康志愿者中单次和多次递增口服剂量后,肌卡因 M3 受体阳性异构调节剂 ASP8302 的安全性、耐受性、药代动力学和药效学。
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-08-09 DOI: 10.1002/cpdd.1460
Shin Takusagawa, Nicoline Treijtel, Masako Saito, Ingrid Michon, Daisuke Miyatake, Fumio Osaki, Sayuri Guro, Tomasso Fadini, Hisakuni Sekino, Marlous Aarden-Bakker, Kentaro Kuroishi, Jan Willem Olivier van Till, Dorien Groenendaal-van de Meent, Michiel de Vries
{"title":"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Muscarinic M3 Receptor-Positive Allosteric Modulator ASP8302 Following Single and Multiple Ascending Oral Doses in Healthy Volunteers","authors":"Shin Takusagawa,&nbsp;Nicoline Treijtel,&nbsp;Masako Saito,&nbsp;Ingrid Michon,&nbsp;Daisuke Miyatake,&nbsp;Fumio Osaki,&nbsp;Sayuri Guro,&nbsp;Tomasso Fadini,&nbsp;Hisakuni Sekino,&nbsp;Marlous Aarden-Bakker,&nbsp;Kentaro Kuroishi,&nbsp;Jan Willem Olivier van Till,&nbsp;Dorien Groenendaal-van de Meent,&nbsp;Michiel de Vries","doi":"10.1002/cpdd.1460","DOIUrl":"10.1002/cpdd.1460","url":null,"abstract":"<p>ASP8302 is an orally administered positive allosteric modulator of the muscarinic M<sub>3</sub> receptor. Two Phase 1 studies were conducted, a first-in-human study in Europe and a Japanese phase 1 study. Both were randomized, participant- and investigator-blinded, placebo-controlled, single and multiple ascending oral doses, parallel group, clinical studies in healthy volunteers. Both studies evaluated safety and pharmacokinetics and also included salivary secretion and pupil diameter as pharmacodynamic assessments. There were no deaths, serious adverse events, or treatment-emergent adverse events reported leading to study discontinuation. There were no clinically relevant findings in any of the laboratory, vital signs, electrocardiogram assessments, or photosensitivity testing following multiple administration of up to 150 mg or up to 140 mg once daily for 14 days in the European first-in-human and Japanese Phase 1 study, respectively. The pharmacokinetics of ASP8302 were approximately linear over the dose range studied. There was no evidence of drug accumulation upon repeated dosing. In both studies, ASP8302 showed a dose-dependent pharmacodynamic effect on saliva production at doses from 100 mg onward, which was maintained during repeated dosing. No effect was observed on pupil diameter. These data supported progression of ASP8302 into Phase 2 clinical trials for further clinical development.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1130-1142"},"PeriodicalIF":1.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906127","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 of Naloxegol in Pediatric Subjects Receiving Opioids 接受阿片类药物治疗的儿科受试者体内纳洛酮的群体药代动力学。
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-08-07 DOI: 10.1002/cpdd.1457
Matthew W. Hruska, Mary Ann Mascelli, Sam Liao, Lori Liao, Patrick Davies, Jennifer Kong, Douglas A. Marsteller
{"title":"Population Pharmacokinetics of Naloxegol in Pediatric Subjects Receiving Opioids","authors":"Matthew W. Hruska,&nbsp;Mary Ann Mascelli,&nbsp;Sam Liao,&nbsp;Lori Liao,&nbsp;Patrick Davies,&nbsp;Jennifer Kong,&nbsp;Douglas A. Marsteller","doi":"10.1002/cpdd.1457","DOIUrl":"10.1002/cpdd.1457","url":null,"abstract":"<p>The pharmacokinetics (PK) of naloxegol were characterized in pediatric subjects, aged 6 months or older to less than 18 years who either have or are at risk of developing opioid-induced constipation following single dose administration. Subjects grouped as aged 12 years or older to less than 18 years, 6 months or older to less than 12 years, and 6 months or older to less than 6 years, received a single oral dose of naloxegol at doses that were estimated to achieve plasma exposures comparable to adult 12.5- or 25-mg doses. Intensive and sparse plasma naloxegol samples were collected to assess naloxegol concentrations. Data were combined with previously collected adult PK data and used to estimate PK parameters using population PK analyses. Naloxegol PK was described using a 2-compartment model with Weibull-type absorption. Neither age nor body weight was identified as a significant covariate indicating similar PK properties in adult and pediatric subjects. PK estimates in the youngest age group were approximately 80% less than those in adults (12.5-mg equivalent dose). Exposures in the other pediatric groups were similar to those in adult equivalent doses. The PK of naloxegol were characterized as linear over the dose range, with no clinically significant covariates and comparable PK characteristics in adults and pediatric subjects aged 6 months or older.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"974-984"},"PeriodicalIF":1.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896965","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
Absorption, Metabolism, and Excretion of [14C]-Labeled Anaprazole: A New Proton Pump Inhibitor, After a Single Oral Administration in Healthy Chinese Male Subjects 一种新型质子泵抑制剂--[14C]标记的阿那普拉唑在中国男性健康受试者中单次口服后的吸收、代谢和排泄:一种新型质子泵抑制剂在中国男性健康受试者口服一次后的吸收、代谢和排泄。
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-08-05 DOI: 10.1002/cpdd.1458
Lijun Xie, Yanjun Xu, Wei Liu, Chen Zhou, Lian Guo, Sufeng Zhou, Chen Zhang, Juan Chen, Bei Zhu, Sijia Ding, Huan Li, Lingling Zhang, Li Wang, Lingmei Xu, Feng Shao, Lu Wang
{"title":"Absorption, Metabolism, and Excretion of [14C]-Labeled Anaprazole: A New Proton Pump Inhibitor, After a Single Oral Administration in Healthy Chinese Male Subjects","authors":"Lijun Xie,&nbsp;Yanjun Xu,&nbsp;Wei Liu,&nbsp;Chen Zhou,&nbsp;Lian Guo,&nbsp;Sufeng Zhou,&nbsp;Chen Zhang,&nbsp;Juan Chen,&nbsp;Bei Zhu,&nbsp;Sijia Ding,&nbsp;Huan Li,&nbsp;Lingling Zhang,&nbsp;Li Wang,&nbsp;Lingmei Xu,&nbsp;Feng Shao,&nbsp;Lu Wang","doi":"10.1002/cpdd.1458","DOIUrl":"10.1002/cpdd.1458","url":null,"abstract":"<p>Anaprazole is a proton pump inhibitor. This study aims to elucidate absorption, metabolism, and excretion pathways of anaprazole sodium in the human body. A total of 4 healthy Chinese male subjects were administered a single oral dose of 20 mg/100 µCi of [<sup>14</sup>C]-anaprazole sodium enteric-coated capsules. The whole blood, plasma, and excreta were analyzed for a total radioactivity (TRA) and metabolite profile. The cumulative radioactivity excretion rate was 93.2%, with 53.3% and 39.9% of the radioactive dose excreted in urine and feces, respectively, and 91.6% of dose recovered within 96 hours after dosing. The parent drug, anaprazole, showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism. Overall, 35 metabolites were identified in plasma, urine, and fecal samples. Anaprazole was the most abundant component in plasma followed by the thioether M8-1, accounting for 28.3% and 16.6%, respectively, of the plasma TRA. Thioether carboxylic acid XZP-3409 (26.3% of urine TRA) and XZP-3409 oxidation and dehydrogenation product M417a (15.1% of fecal TRA) were the major metabolites present in urine and feces, respectively. Anaprazole was undetectable in urine, while fecal samples showed traces (0.07% dose). Blood/plasma ratios of the radioactivity (approximately 0.60) remained consistent over time. Anaprazole showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism, and cytochrome P450 3A4 also contributed to its metabolism in healthy individuals.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1115-1122"},"PeriodicalIF":1.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative Bioavailability of a Novel Fixed-dose Combination Etoricoxib and Tramadol 新型固定剂量复方药物依托考昔和曲马多的生物利用度比较
IF 1.5 4区 医学
Clinical Pharmacology in Drug Development Pub Date : 2024-07-31 DOI: 10.1002/cpdd.1456
Lourdes Garza-Ocañas, Christian T. Badillo-Castaneda, Sandra L. Montoya Eguía, María T. Zanatta-Calderón, Julia D. Torres Garza, Marco Vinicio Gómez-Meza, José G. Sander-Padilla, Laura A. Lugo-Sánchez, Kevin F. Rios-Brito, Yulia Romero-Antonio, Jorge González-Canudas
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