Clinical Pharmacology in Drug Development最新文献_第2页

Evaluation of the Effect of Momelotinib on Cardiac Repolarization: A Thorough QT Study

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-23 DOI: 10.1002/cpdd.1509

Georgios Vlasakakis, Yolanda Alvarez, Timothy Hart, Yu Liu Ho, Catherine Ellis

{"title":"Evaluation of the Effect of Momelotinib on Cardiac Repolarization: A Thorough QT Study","authors":"Georgios Vlasakakis, Yolanda Alvarez, Timothy Hart, Yu Liu Ho, Catherine Ellis","doi":"10.1002/cpdd.1509","DOIUrl":"10.1002/cpdd.1509","url":null,"abstract":"A randomized, partially blinded, placebo-controlled, crossover study in 48 healthy adults assessed the effect of momelotinib on the heart rate-corrected QT interval (QTc) using the Fridericia formula (QTcF). QTc was evaluated for momelotinib 200 mg (therapeutic dose), momelotinib 800 mg (supratherapeutic dose), moxifloxacin 400 mg (positive control), and placebo. Pharmacokinetic profiles of momelotinib and its active metabolite M21 were evaluated. Momelotinib did not prolong QTcF, as the upper bounds of the 2-sided 90% confidence intervals (CIs) for the mean difference between doses of momelotinib and placebo were <10 milliseconds at all time points. The lower limit of the 2-sided 98% CI for the mean difference in QTcF between moxifloxacin versus placebo was >5 milliseconds at 2, 3, and 4 hours after dosing, demonstrating assay sensitivity. There was no positive relationship between momelotinib plasma concentrations and QTcF. Adverse events (AEs) were more frequent with the supratherapeutic dose of momelotinib, but none were considered severe. There were no deaths, serious AEs, or AEs leading to study discontinuation. Neither therapeutic nor supratherapeutic doses of momelotinib led to clinically significant effects on the QTc interval, supporting a negative finding for QTc prolongation from this thorough QT study.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 4","pages":"333-342"},"PeriodicalIF":1.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022482","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 Mass Balance Study of Pizuglanstat: An Investigational Hematopoietic Prostaglandin D Synthase Inhibitor pizuganstat的1期质量平衡研究：一种研究性造血前列腺素D合成酶抑制剂。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-22 DOI: 10.1002/cpdd.1504

Ryuzo Hanada, Toru Takenaka

{"title":"Phase 1 Mass Balance Study of Pizuglanstat: An Investigational Hematopoietic Prostaglandin D Synthase Inhibitor","authors":"Ryuzo Hanada, Toru Takenaka","doi":"10.1002/cpdd.1504","DOIUrl":"10.1002/cpdd.1504","url":null,"abstract":"Pizuglanstat is a novel hematopoietic prostaglandin D synthase inhibitor and investigational treatment for Duchenne muscular dystrophy. This Phase 1 mass balance study aimed to characterize the absorption, metabolism, and excretion of carbon-14 (14C)-labeled pizuglanstat in healthy adults (ClinicalTrials.gov, NCT04825431). After administering a single oral dose of [14C]pizuglanstat solution containing 400 mg of pizuglanstat and 1 megabecquerel of radioactivity to 6 healthy men (median age, 26 years), pizuglanstat in plasma reached a maximal concentration after a median of 0.5 hour and declined with a geometric mean half-life of 7.7 hours. Pizuglanstat and its metabolites were primarily excreted via the fecal route; on average, 66.1% of administered radioactivity was excreted in feces after 168 hours, compared with 32.2% excreted in urine. Pizuglanstat was mostly present as the unchanged parent molecule in plasma, urine, and feces, while the sulfate conjugate of hydroxyl pizuglanstat was the major metabolite in each sample type. Two adverse drug reactions of urticaria were reported in 2 participants (33.3%); both events were nonsevere and manageable with treatment, and no other clinically significant safety events were observed. Overall, this study provides important pharmacokinetic, mass balance, and safety data to support the development of pizuglanstat as a new treatment for Duchenne muscular dystrophy.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"200-208"},"PeriodicalIF":1.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001550","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 Study of Bedaquiline Fumarate Tablets in Healthy Chinese Subjects 富马酸贝达喹啉片在健康人体内的生物等效性研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-19 DOI: 10.1002/cpdd.1515

Man Yang, Yingzi Pei, Chen Chen, Jian Xi, Yue Xia, Shuyu Zhang, Huichen Liu, Aimin Li

{"title":"Bioequivalence Study of Bedaquiline Fumarate Tablets in Healthy Chinese Subjects","authors":"Man Yang, Yingzi Pei, Chen Chen, Jian Xi, Yue Xia, Shuyu Zhang, Huichen Liu, Aimin Li","doi":"10.1002/cpdd.1515","DOIUrl":"10.1002/cpdd.1515","url":null,"abstract":"Bedaquiline fumarate tablets are a novel oral antimycobacterial drug. This study assessed the bioequivalence of a generic bedaquiline fumarate tablet compared to a reference tablet under fasting (n = 44) and fed (n = 24) conditions. Conducted as a single-center, randomized, open-label, 2-sequence, crossover trial, 68 participants were randomly assigned to receive a 100-mg dose of either the test or reference tablet, with a 42-day washout period between doses. Blood samples were collected at prespecified time points from 0 hour (before administration) to 984 hours after administration. Plasma concentrations of bedaquiline were measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Safety was monitored throughout the study. Key pharmacokinetic parameters included maximum plasma concentration, area under the plasma concentration-time curve (AUC) from 0 to 72 hours, AUC from time 0 to the last measurable concentration, AUC from 0 to 336 hours, and AUC from time 0 to infinity. The 90% confidence intervals for the geometric mean ratios of the test/reference formulations for maximum plasma concentration, AUC from 0 to 72 hours, AUC from 0 to 336 hours, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity fell within the bioequivalence acceptance range of 80%-125%. confirming bioequivalence between the 2 formulations in healthy Chinese volunteers. Moreover, a high-fat diet can significantly elevate the exposure of bedaquiline. No serious adverse events occurred, and both formulations were well tolerated across all participants.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"263-269"},"PeriodicalIF":1.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001537","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 Between 2 Oral Tablet Formulations of Rivaroxaban 20 mg in Healthy Chinese Subjects. 利伐沙班20mg两种口服片剂在健康人群中的生物等效性及食用效应评价。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-19 DOI: 10.1002/cpdd.1511

Kaixian Tang, Yingrong Chen, Jue Mei, Hui Bo, Qing Liu, Wei Wang, Min Xu, Qiuyue Jin, Shuixin Yang

{"title":"Bioequivalence and Food Effect Assessment Between 2 Oral Tablet Formulations of Rivaroxaban 20 mg in Healthy Chinese Subjects.","authors":"Kaixian Tang, Yingrong Chen, Jue Mei, Hui Bo, Qing Liu, Wei Wang, Min Xu, Qiuyue Jin, Shuixin Yang","doi":"10.1002/cpdd.1511","DOIUrl":"https://doi.org/10.1002/cpdd.1511","url":null,"abstract":"To evaluate the bioequivalence and safety of oral rivaroxaban tablets between a test formulation and a reference formulation in healthy Chinese subjects, a randomized, open, 2-formulation, 4-cycle, complete repeat crossover study was conducted under both fasting and fed states. Thirty-six healthy participants were enrolled separately for the fasting and fed groups, and each subject received a single oral dose of 20 mg of the test or reference formulation of rivaroxaban tablets per cycle. Blood samples were collected at specified intervals, and rivaroxaban was analyzed using liquid chromatography-tandem mass spectrometry. Under fasting and fed conditions, the 90% confidence intervals (CIs) for the geometric mean ratios of the maximum concentration (Cmax), the area under the plasma concentration-time curve from time 0 to the last measurable time point (AUC0-t), and the area under the curve extrapolated to infinity from time 0 (AUC0-∞) all fell within the 80%-125% CI, and the upper limit of the 90% CIs for the test-to-reference ratio of the within-subject variability was <2.5. This indicated that the test formulation of rivaroxaban is bioequivalent to the reference formulation. Compared to the fasted state, the Cmax, AUC0-t, and AUC0-∞ of rivaroxaban increased significantly by factors of 2, 1.6, and 1.5, respectively, following oral administration of 20 mg of rivaroxaban in the fed state. This suggests that a high-fat diet significantly enhances the exposure to rivaroxaban. No serious adverse events were reported under fasting or fed conditions.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001492","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 Pharmacokinetics and Bioequivalence of 2 Formulations of Bosentan Dispersible Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions. 两种波生坦分散片制剂在空腹和空腹条件下的比较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 : 2025-01-19 DOI: 10.1002/cpdd.1516

Zhaoming Huang, Panpan Yu, Jiawei Hu, Wanyong Zhang

{"title":"Comparative Pharmacokinetics and Bioequivalence of 2 Formulations of Bosentan Dispersible Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.","authors":"Zhaoming Huang, Panpan Yu, Jiawei Hu, Wanyong Zhang","doi":"10.1002/cpdd.1516","DOIUrl":"https://doi.org/10.1002/cpdd.1516","url":null,"abstract":"Bosentan is a dual endothelin receptor antagonist widely used in the treatment of pulmonary artery hypertension. However, there are few reports on the pharmacokinetics (PK) and bioequivalence of bosentan dispersible tablets (32 mg) in the Chinese population. This study aimed to evaluate the PK characteristics and bioequivalence of the test and reference formulations of bosentan dispersible tablets in healthy Chinese volunteers under fasting and fed conditions. A randomized, single-dose, 2-sequence, 2-period crossover study (fasting) and a 4-period replicate crossover study (fed) were conducted with 48 and 30 healthy volunteers, respectively. The bosentan plasma concentrations were measured by a validated ultra-performance liquid chromatography coupled with a tandem mass spectrometry method, and PK parameters were analyzed using noncompartmental methods. The bioequivalence statistical analysis showed that 90% confidence intervals for the geometric mean ratios of peak plasma concentration, area under the concentration-time curve (AUC) from time zero to the last measurable concentration, and AUC from time zero to infinity for the test and reference formulations were within the bioequivalence range of 80%-125% under both fasting and fed conditions. After the administration of bosentan dispersible tablets under fed conditions, the systemic exposure (based on AUC from time zero to infinity) was increased by approximately 15%-20%. These findings confirm the bioequivalence of the 2 formulations, and both formulations were well tolerated, with no safety-related adverse events reported. Given the wide therapeutic dose range of bosentan dispersible tablets for the treatment of pulmonary artery hypertension in children, the impact of food on its PK is not considered clinically significant.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001545","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 2 Products of Fluticasone Propionate Nasal Spray in Healthy Chinese Subjects. 两种产品丙酸氟替卡松鼻喷雾剂在健康人体内的药代动力学及生物等效性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-19 DOI: 10.1002/cpdd.1507

Pengkai Wang, Yuan Li, Bing Xu, Ping Zhang, Chang Cui, Xin Li

引用次数: 0

A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects. 一项评估单次递增口服多达维易的安全性、耐受性和药代动力学以及食物对健康成人多达维易生物利用度影响的1期随机研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-16 DOI: 10.1002/cpdd.1512

Shamia L Faison, Joelle Batonga, Thangam Arumugham, Angela Bartkus, Marion Morrison, Mark J Mullin, Tim Tippin, Odin Naderer

{"title":"A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects.","authors":"Shamia L Faison, Joelle Batonga, Thangam Arumugham, Angela Bartkus, Marion Morrison, Mark J Mullin, Tim Tippin, Odin Naderer","doi":"10.1002/cpdd.1512","DOIUrl":"https://doi.org/10.1002/cpdd.1512","url":null,"abstract":"Dordaviprone (ONC201) is a novel, small molecule imipridone with antitumor effects in glioma patients. This study evaluated the pharmacokinetics and safety of dordaviprone following single escalating doses (Part A), as a capsule content mixed with applesauce or Gatorade (sports drink) [Part B1]), and with or without food [Part B2]. The most common treatment-emergent adverse events pooled across study parts (Parts A, B1, and B2) were headache, dizziness, and headache, respectively; all were mild. Systemic dordaviprone exposure increased dose proportionally following administration of 125-625 mg of dordaviprone. Following dordaviprone capsule contents sprinkled on applesauce or dissolved in sports drink, the geometric mean ratios, and 90% confidence intervals (CIs) of the dordaviprone area under the concentration versus time curve (AUC) fell within the bioequivalence (BE) limits of 80.00%-125.00%; however, for Cmax the 90% CI lower limit (0.70) fell below BE limits when sprinkled on applesauce. The geometric mean ratios and 90% CIs of dordaviprone administered under fed versus fasted conditions fell within BE limits of 80.00%-125.00% for the AUC, indicating no food effect on total exposure; however, maximum concentration (Cmax) (90% CI 0.55, 0.67) fell below BE limits.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001461","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

Equivalence of Biosimilarity in Pharmacokinetic and Pharmacodynamic Properties of Recombinant Human Insulin Aspart 重组人胰岛素天冬氨酸的药代动力学和药效学特性的生物相似性等效性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-15 DOI: 10.1002/cpdd.1510

Sneha A. Dongre, Gauri A. Kulkarni, Damodar Thapa, Nikhil Ghade, Jeseena Lona, Hiren Prajapati, Hiren Mehta, Swati Guttikar, Archana R. Krishnan, Sanjay M. Sonar

{"title":"Equivalence of Biosimilarity in Pharmacokinetic and Pharmacodynamic Properties of Recombinant Human Insulin Aspart","authors":"Sneha A. Dongre, Gauri A. Kulkarni, Damodar Thapa, Nikhil Ghade, Jeseena Lona, Hiren Prajapati, Hiren Mehta, Swati Guttikar, Archana R. Krishnan, Sanjay M. Sonar","doi":"10.1002/cpdd.1510","DOIUrl":"10.1002/cpdd.1510","url":null,"abstract":"Insulin aspart, a rapid-acting analog, achieves faster subcutaneous absorption than regular insulin. This study aimed to demonstrate equivalence in the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of Recombinant Human Insulin Aspart from BioGenomics Limited (as test) and Novo-Nordisk (as reference) in healthy adult males. This was a double-blind, randomized, cross-over study, assessing PK and PD parameters under fasting conditions. Participants received either 0.2 U/kg of test or reference product via a subcutaneous route in the abdominal area. PK parameters included maximum serum concentration (Cmax), area under the curve [(AUC[0-t]) and (AUC [0-∞])], time to maximum serum concentration (Tmax), and half-life (t½). PD parameters included amount of glucose infused (Gtot), maximum glucose infusion rate (Rmax), time of Rmax (tRmax), late time of half-maximal glucose infusion rate (tRmax50), time of first measured glucose infusion rate (tonset), and cessation of glucose infusion/clamp (tRlast). Seventy subjects between 18 and 45 years of age and body mass index between 18 and 27 kg/m2 were enrolled. The 90% confidence intervals (CIs) for Cmax, AUC[0-t], AUC [0-∞] for insulin, and the 95% CIs for Gtot, Rmax for glucose were within 80%-125% as required to assess test-reference bioequivalence. No serious adverse events were observed. Both the preparations showed bioequivalence under fasting conditions with a similar safety profile.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"209-216"},"PeriodicalIF":1.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001548","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 Drug–Drug Interaction Study of Mobocertinib and Midazolam, a Cytochrome P450 3A Substrate, in Patients With Advanced Non–Small Cell Lung Cancer Mobocertinib和Midazolam（细胞色素P450 3A底物）在晚期非小细胞肺癌患者中的药物相互作用研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-15 DOI: 10.1002/cpdd.1500

Michael J. Hanley, Steven Zhang, Nick Pavlakis, Ross A. Soo, Anthonie J. van der Wekken, Vinod Ganju, Adela Piña, Qi Dong, Neeraj Gupta

{"title":"A Drug–Drug Interaction Study of Mobocertinib and Midazolam, a Cytochrome P450 3A Substrate, in Patients With Advanced Non–Small Cell Lung Cancer","authors":"Michael J. Hanley, Steven Zhang, Nick Pavlakis, Ross A. Soo, Anthonie J. van der Wekken, Vinod Ganju, Adela Piña, Qi Dong, Neeraj Gupta","doi":"10.1002/cpdd.1500","DOIUrl":"10.1002/cpdd.1500","url":null,"abstract":"Mobocertinib is a kinase inhibitor designed to selectively target epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in non-small cell lung cancer. This drug–drug interaction study assessed the effect of multiple-dose administration of mobocertinib on the pharmacokinetics (PK) of midazolam, a sensitive cytochrome P450 3A substrate. Patients with locally advanced or metastatic non-small cell lung cancer refractory/intolerant to standard available therapy were enrolled. In Cycle 1 (Part A; PK cycle), a single 3-mg oral dose of midazolam was administered on Days 1 and 24, and a single 1-mg intravenous dose of midazolam was administered on Days 2 and 25. Mobocertinib 160 mg once daily was administered orally on Days 3-30. After Cycle 1, patients could continue receiving mobocertinib in 28-day cycles in Part B of the study. The study objective was to characterize the effect of mobocertinib on the single oral- and intravenous-dose PK of midazolam. Safety and exploratory efficacy were also assessed. Twenty-six patients were enrolled, and 13 patients were PK-evaluable. Safety findings were consistent with the known safety profile of mobocertinib, and diarrhea was the only Grade 3 or higher treatment-related adverse event observed in more than 2 patients. Two of 16 patients with EGFR exon 20 insertion mutations were confirmed responders per investigator. Coadministration of mobocertinib decreased the area under the plasma concentration–time curve from time zero to infinity of oral and intravenous midazolam by approximately 32% and 16%, respectively (geometric least-squares mean ratios of 0.676 and 0.837, respectively).","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"252-262"},"PeriodicalIF":1.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1500","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001454","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

A Comparative Analysis of the Pharmacodynamic and Pharmacokinetic Properties of 2 Controlled-Release Formulations Versus a Marketed Orlistat Product 两种控释制剂与上市奥利司他产品的药效学和药代动力学特性比较分析。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-09 DOI: 10.1002/cpdd.1503

Stefan Grudén, Anders Forslund, Helena Litorp, Sandra Kuusk, Göran Alderborn, Arvid Söderhäll, Ulf Holmbäck

{"title":"A Comparative Analysis of the Pharmacodynamic and Pharmacokinetic Properties of 2 Controlled-Release Formulations Versus a Marketed Orlistat Product","authors":"Stefan Grudén, Anders Forslund, Helena Litorp, Sandra Kuusk, Göran Alderborn, Arvid Söderhäll, Ulf Holmbäck","doi":"10.1002/cpdd.1503","DOIUrl":"10.1002/cpdd.1503","url":null,"abstract":"A new modified-release oral formulation combines acarbose and orlistat (MR-OA) to enhance efficacy and reduce adverse effects through controlled drug release. This study aims to compare the pharmacodynamic properties of the orlistat component of MR-OA (MR-O) with a conventional orlistat product, Xenical (Conv-O), analyzing the percentage of fecal fat excretion. In addition, the pharmacokinetic properties of the complete formulation, MR-OA, were compared with Conv-O. In Part I of the study, 20 healthy volunteers were randomized in a single-blind, crossover trial to take MR-O or Conv-O (120-mg orlistat) 3 times daily for 9 days. Fecal fat was measured at baseline and after each treatment. MR-O and Conv-O similarly increased fecal fat percentage from 3.8% to 13.5%, confirming pharmacodynamic equivalence. Adverse events were few and generally rated as mild. In Part II, participants received MR-OA and then Conv-O, with blood samples collected for 12 hours to measure orlistat and acarbose levels. Orlistat's peak concentration stayed below 5 ng/mL, and acarbose plasma levels were mostly undetectable, indicating minimal systemic absorption. This shows that the new weight loss product MR-OA retains the dietary energy loss pathway used in Conv-O. Consistent with previous studies, minimal systemic absorption of orlistat and acarbose was observed for MR-OA, confirming that no significant alteration of the original substances occurs when modifying their release.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 4","pages":"304-310"},"PeriodicalIF":1.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945653","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