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

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

Determination of the Bioavailability of 3 Intranasal Formulations of Azelastine Hydrochloride in Healthy Male Volunteers 3种盐酸氮扎elastine鼻内制剂在健康男性体内的生物利用度测定。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-09 DOI: 10.1002/cpdd.1498

Jean Bousquet, Ludger Klimek, Mark Liu, Duc Tung Nguyen, Rajesh Kumar Ramalingam, Georgio Walter Canonica, William E. Berger

{"title":"Determination of the Bioavailability of 3 Intranasal Formulations of Azelastine Hydrochloride in Healthy Male Volunteers","authors":"Jean Bousquet, Ludger Klimek, Mark Liu, Duc Tung Nguyen, Rajesh Kumar Ramalingam, Georgio Walter Canonica, William E. Berger","doi":"10.1002/cpdd.1498","DOIUrl":"10.1002/cpdd.1498","url":null,"abstract":"The primary objective of the study was to determine the bioavailability of 2 new formulations of azelastine (AZE) hydrochloride (0.10% and 0.15% AZE) containing sorbitol and sucralose compared with the commercially available 0.10% AZE. This study was performed in healthy volunteers based on the pharmacokinetic parameters maximum plasma concentration and area under the plasma concentration–time curve from time zero to the last measurable concentration. This was a Phase 1, open-label, single-center, randomized, parallel-group study. Subjects were randomized to 1 of 3 treatment groups: (1) 0.10% AZE (treatment A), (2) 0.15% AZE (treatment B) (Groups 1 and 2 both containing sorbitol and sucralose), and (3) the commercially available 0.10% AZE (treatment C). A total of 54 subjects were randomized and received treatment A, B, or C. Maximum plasma concentration and area under the plasma concentration–time curve were similar when compared in treatments A and C (0.1%) for AZE and its metabolite, desmethylazelastine. The most frequently reported adverse events were rhinorrhea (5.6%) and sneezing (5.6%).","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"217-222"},"PeriodicalIF":1.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945590","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 2 Formulations of Fluticasone Nasal Spray in Healthy Chinese Volunteers 氟替卡松鼻喷雾剂两种剂型在中国健康志愿者体内的生物等效性研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-09 DOI: 10.1002/cpdd.1505

Gang Chen, Zejuan Wang, Xiaona Liu, Aihua Du, Min Li, Yanan Zhang, Dan Zhang, Xiaolin Wang, Xueyan Li, Wei Cong, Jin Wang

{"title":"Bioequivalence Study of 2 Formulations of Fluticasone Nasal Spray in Healthy Chinese Volunteers","authors":"Gang Chen, Zejuan Wang, Xiaona Liu, Aihua Du, Min Li, Yanan Zhang, Dan Zhang, Xiaolin Wang, Xueyan Li, Wei Cong, Jin Wang","doi":"10.1002/cpdd.1505","DOIUrl":"10.1002/cpdd.1505","url":null,"abstract":"This study aimed to evaluate the pharmacokinetic characteristics, safety, and bioequivalence of 2 formulations of fluticasone nasal spray in healthy Chinese subjects. A single-center, randomized, open-label, single-dose, 2-formulation, 2-sequence, 2-period crossover bioequivalence study was conducted under fasting conditions. A total of 120 healthy male and female subjects were enrolled, of which 119 subjects completed the entire study. The main pharmacokinetic parameters of the parent drug, fluticasone propionate (FP), in plasma were as follows: For the test formulation, maximum plasma concentration (Cmax) was 10.3 pg/mL, area under the plasma concentration–time curve from time zero to the last quantifiable concentration (AUC0-t) was 65.6 pg•h/mL, and area under the plasma concentration–time curve from time zero to infinity (AUC0-∞) was 86.4 pg•h/mL. For the reference formulation: Cmax was 8.80 pg/mL, AUC0-t was 58.2 pg•h/mL, and AUC0-∞ was 75.2 pg•h/mL. The 90% confidence intervals of the geometric means for AUC0-t, AUC0-∞, and Cmax between the 2 formulations were 105%-120%, 103%-120%, and 112%-124%, respectively. The results show that the test and reference formulations were well tolerated, with no serious adverse events reported. According to the criteria for bioequivalence, the FP nasal spray (test formulation) is bioequivalent to the reference formulation.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"270-275"},"PeriodicalIF":1.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945656","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 Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma 转移性胰腺导管腺癌患者certe肽的群体药代动力学模型。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2025-01-09 DOI: 10.1002/cpdd.1502

Alex Winning, William K. Sietsema, Kristen K. Buck, Abigail Linsmeier, Pawel Wiczling

{"title":"Population Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma","authors":"Alex Winning, William K. Sietsema, Kristen K. Buck, Abigail Linsmeier, Pawel Wiczling","doi":"10.1002/cpdd.1502","DOIUrl":"10.1002/cpdd.1502","url":null,"abstract":"Certepetide (aka LSTA1 and CEND-1) is a novel cyclic tumor-targeting internalizing arginyl glycylaspartic acid peptide being developed to treat solid tumors. Certepetide is designed to overcome existing challenges in treating solid tumors by delivering co-administered anticancer drugs into the tumor while selectively depleting immunosuppressive T cells, enhancing cytotoxic T cells in the tumor microenvironment, and inhibiting the metastatic cascade. A population pharmacokinetic (PK) analysis was conducted to characterize the concentration-time profile of patients with metastatic exocrine pancreatic cancer receiving certepetide in combination with nab-paclitaxel and gemcitabine, and to investigate the effects of clinically relevant covariates on PK parameters. The PK of certepetide was characterized by a 2-compartment model with linear elimination and a proportional residual error structure. Body weight and baseline creatinine clearance (CrCL) were found to have statistically significant effects on central and peripheral volume (Vc and Vp) and clearance (CL) parameters, respectively, during model development and were included as covariate effects in the final PK model. Forest plots demonstrated a potentially clinically meaningful impact of high body weight (100 kg) on certepetide exposure (steady-state maximum concentration [Cmax,ss] and area under the concentration-time curve [AUCss]), as well as low and high CrCL (50 and 150 mL/min) on AUCss. Exposure predictions illustrated a relationship between certepetide exposure (AUCss) and renal function, with increasing exposure and decreasing CL of certepetide observed with worsening renal function. Modeling will strengthen the understanding of certepetide's PKs and will inform dose optimization in ongoing drug development activities.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 3","pages":"240-251"},"PeriodicalIF":1.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945619","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