Clinical Pharmacology in Drug Development最新文献

{"title":"Bioequivalence and Safety of Two Oseltamivir Phosphate for Oral Suspension in Healthy Chinese Subjects Under Fasting and Fed Conditions: A Randomized, Open‑Label, Single‑Dose, Crossover Study.","authors":"Yu Peng, Ming Zhou, Hegui Yan, Zhixiang Pan, Yiyi Wang, Shuang Wei, Guan Liu","doi":"10.1002/cpdd.1612","DOIUrl":"https://doi.org/10.1002/cpdd.1612","url":null,"abstract":"<p><p>This randomized, open-label, single-dose crossover study evaluated the bioequivalence of a Chinese-manufactured oseltamivir phosphate oral suspension (7.5 mg/12.5 mL) against Tamiflu under fasting and fed conditions. A total of 42 healthy Chinese adults were enrolled in each group, with 39 completing the fasting group (3 withdrew) and 40 completing the fed group (1 withdrew in washout, 1 lost to follow-up). Plasma concentrations of oseltamivir and its active metabolite oseltamivir carboxylate were measured via LC-MS/MS, and pharmacokinetic parameters were calculated using non-compartmental models. The 90% confidence intervals of key parameters fell within the 80.00-125.00% range, confirming bioequivalence. No serious adverse events occurred, indicating similar safety profiles. The test formulation is bioequivalent to Tamiflu under both fasting and fed conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225045","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}

{"title":"Model-Informed Drug Development in Early-Phase Development: Navigating Complexity With Quantitative Clarity","authors":"Amalia M. Issa","doi":"10.1002/cpdd.1607","DOIUrl":"https://doi.org/10.1002/cpdd.1607","url":null,"abstract":"&lt;p&gt;Model-informed drug development (MIDD) has evolved from a promising innovation to a regulatory imperative in drug development. Over the past year, the regulatory landscape shifted. The Food and Drug Administration (FDA) finalized guidance on oncology dose optimization under Project Optimus&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; and institutionalized its MIDD Paired Meeting Program,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; while ICH issued E11A for pediatric extrapolation&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; and released a draft guideline M15, developed under ICH auspices, on generalized MIDD principles.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; These developments collectively transform early drug development: the goal is no longer just identifying a tolerated dose but quantitatively justifying optimal dosing for pivotal trials. By integrating pharmacokinetics (PK), pharmacodynamics (PD), systems pharmacology, and real-world data, MIDD reduces development risks, accelerates first-in-human studies, and enables rational dose selection. Its expanding influence on decision-making underscores its role not only as a technical methodology but as a paradigm shift in early-phase development strategy.&lt;/p&gt;&lt;p&gt;In the last decade, the utility of MIDD has expanded significantly, driven by advances in computational modeling and an increasingly favorable regulatory environment. The FDA and the European Medicines Agency (EMA) have articulated frameworks encouraging the use of MIDD in early development, with the FDA's &lt;i&gt;MIDD Pilot Program&lt;/i&gt; serving as a cornerstone initiative fostering sponsor–regulator dialogue.&lt;span&gt;&lt;sup&gt;3, 5-7&lt;/sup&gt;&lt;/span&gt; In 2025, such efforts have matured, with MIDD now recognized as central to regulatory submissions in oncology, rare diseases, and immunology.&lt;/p&gt;&lt;p&gt;Recent literature emphasizes that MIDD enables the translation of preclinical data into clinically relevant predictions with unprecedented precision. For example, Ren et al&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; highlight how PK/PD modeling refines dose optimization strategies in discovery and development, allowing earlier identification of optimal therapeutic windows.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This has relevance in first-in-human trials, where dose escalation strategies can now be informed by quantitative predictions rather than empirical trial-and-error. This shift reframes early-phase development from “first safe dose” thinking to “first scientifically informative dose.”&lt;/p&gt;&lt;p&gt;1. &lt;i&gt;First-in-Human Dose Prediction&lt;/i&gt;. Physiologically based pharmacokinetic (PBPK) modeling has revolutionized first-in-human dose selection, particularly for biologics and small molecules with complex metabolism. PBPK models incorporate variability in absorption, metabolism, and clearance across virtual populations, offering mechanistic insights that go beyond traditional allometric scaling.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; In oncology and rare diseases, such models are increasingly used to support starting dose rationalization, minimizing both underdosing and toxicity risk","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"14 10","pages":"738-741"},"PeriodicalIF":1.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145196454","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}

{"title":"Pharmacokinetics, Bioequivalence, and Safety of Bromocriptine Mesylate Tablets in HealthyChinese Subjects.","authors":"Huan Song, Yujun Chen, Lianlian Chen, Xianmiao Yin, Huan Li, Fangliang Gan","doi":"10.1002/cpdd.1610","DOIUrl":"https://doi.org/10.1002/cpdd.1610","url":null,"abstract":"<p><p>To investigate the pharmacokinetic characteristics of bromocriptine mesylate tablets in healthy Chinese subjects and to assess their bioequivalence and safety. A randomized, open-label, single-dose, four-period, two-sequence, complete crossover study was conducted. Forty healthy volunteers were enrolled and administered a single oral dose of 2.5 mg of either the test formulation (T) or the reference formulation (R) of bromocriptine mesylate tablets under fed conditions, with a 7-day washout period between treatments. Plasma concentrations of bromocriptine mesylate were measured using ultra-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated using Phoenix WinNonlin software for bioequivalence evaluation. Geometric mean ratios of maximum concentration, the area under the concentration-time curve from time zero to the last measurable concentration, and the area under the concentration-time curve from time zero to infinity were calculated: maximum concentration by reference-scaled average bioequivalence using a 95% upper confidence bound, and the area under the concentration-time curve from time zero to the last measurable concentration and the area under the concentration-time curve from time zero to infinity by average bioequivalence with 90% confidence intervals. Data from the fed trial met the bioequivalence criteria. No serious adverse reactions were observed, indicating that the test and reference bromocriptine mesylate tablets have similar safety profiles under fed conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184740","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}

{"title":"The Pathway to Proof-of-Concept for BNC210, a Negative Allosteric Modulator of the Alpha-7 Nicotinic Acetylcholine Receptor (nAChR), for Treatment of Psychiatric Disease.","authors":"Paul Rolan, Elizabeth Doolin, Dharam Paul, Julia Crossman, Michael Odontiadis, Philippe Danjou, Mark Smith, Spyros Papapetropoulos","doi":"10.1002/cpdd.1609","DOIUrl":"https://doi.org/10.1002/cpdd.1609","url":null,"abstract":"<p><p>BNC210 is an investigational small molecule selective negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor (α7 nAChR). It is an anxiolytic compound with a novel mechanism of action. In a series of Phase 1 clinical trials in healthy volunteers, psychometric test batteries showed that BNC210 did not cause attention, cognition, or memory impairment, negative effects on mood or emotional stability, sedation, or addiction, ruling out undesirable side effects of known anxiolytic compounds. In healthy volunteers, target engagement at the α7 nAChR was demonstrated in a nicotine shift assay using quantitative electroencephalography, and BNC210 demonstrated improvement in panic-like symptoms in a cholecystokinin tetrapeptide panic model. Initial clinical trials used an aqueous suspension formulation of BNC210 to cover a wide dosage range; however, its pharmacokinetic parameters were consistent with solubility-limited absorption and a significant food effect. A dispersible tablet formulation was then developed with improved bioavailability and is being used in Phases 2 and 3 clinical trials. Collectively, the Phase 1 data demonstrated desired properties of BNC210 supporting proof-of-concept clinical trials. BNC210 is currently being developed for acute, as-needed treatment of social anxiety disorder and chronic treatment of post-traumatic stress disorder.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173715","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}

{"title":"A multipart phase 1 study of the safety, pharmacodynamics and pharmacokinetics of ALG-055009, a novel thyroid hormone receptor beta (THR-β) agonist for metabolic dysfunction-associated steatohepatitis (MASH), in healthy participants.","authors":"Hakim Charfi, Benedetta Massetto, Megan Fitzgerald, Kha Le, Stanley Wang, Ifong Kan-Eng, Meenakshi Venkatraman, Naqvi Mohammad, Lawrence Blatt, Tse-I Lin, Sushmita M Chanda, John Fry","doi":"10.1002/cpdd.1606","DOIUrl":"https://doi.org/10.1002/cpdd.1606","url":null,"abstract":"<p><p>ALG-055009 is an oral thyroid hormone receptor beta (THR-β) agonist being evaluated for treating metabolic dysfunction-associated steatohepatitis (MASH). This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALG-055009 and bioavailability/food effect. Part 1 was a single-ascending dose study in healthy participants randomized to ALG-055009 (0.1 to 4.0 mg) or placebo. Part 2 was a multiple-ascending dose study in participants with mild hyperlipidemia randomized to ALG-055009 (0.3 to 1.0 mg) or placebo once daily for 14 days. Part 3 was an open-label study to determine relative bioavailability and food effect of 0.6 mg ALG-055009 solution versus soft gelatin (softgel) capsule formulation. Among 78 participants, ALG-055009 was well tolerated, and most adverse events were mild or moderate with no clinically meaningful safety issues. Transient reductions in thyroid hormone levels were observed with no clinical manifestation of hypo/hyperthyroidism. Plasma ALG-055009 exposure increased in a dose-proportional manner with rapid absorption, low variability, accumulation ranging from 1.6-2.6-fold, and t_1/2 of 20 h. Relative bioavailability of the softgel capsule was 86% versus solution, with no food effect. Dose-dependent decreases in atherogenic lipids and increases in sex hormone binding globulin were observed. These results support further development of ALG-055009 for patients with MASH.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085184","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}

{"title":"Pharmacokinetics and bioequivalence of acetylcysteine granules among Chinese healthy volunteers under fasting and postprandial conditions.","authors":"Jingjing Wang, Wanggang Zhang","doi":"10.1002/cpdd.1605","DOIUrl":"https://doi.org/10.1002/cpdd.1605","url":null,"abstract":"<p><p>This study aimed to evaluate the pharmacokinetics, bioequivalence, and safety for two formulations of acetylcysteine granules in healthy Chinese subjects under fasting and postprandial conditions. A single-center, randomized, open-label, single-dose, two-period, two-sequence crossover study was performed. 34 and 38 healthy Chinese volunteers were enrolled in the fasting and postprandial groups, respectively. Each subject received a single oral dose (0.2 g) of acetylcysteine granules per period either as the test (T) or reference (R) formulation, followed by a 5-day washout interval. Serial blood samples were collected for up to 24 h post-dose in each period, and plasma concentration of acetylcysteine was detected using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Whether under fasting or postprandial conditions, all the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for maximum concentration (C_max), area under the curve from time 0 to the time of the last measurable concentration (AUC_0- _t), and area under the curve from time 0 to infinity (AUC_0-∞) were all found to fall within the bioequivalence range of 80.00-125.00%. Only mild adverse events (AEs) were observed. In the study, the two formulations of acetylcysteine granules were bioequivalent and safe.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052132","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}

{"title":"Pharmacokinetics, Tolerability, and Biomarker Profile of the Neurokinin 3 Receptor Antagonist Fezolinetant in Healthy Japanese Individuals: A 2-Part, Randomized, Phase 1 Study.","authors":"Akira Koibuchi, Megumi Iwai, Kanji Komatsu, Kentaro Kuroishi, Mai Shibata, Masako Saito, Jace Nielsen, Jiayin Huang, Shunji Matsuki","doi":"10.1002/cpdd.1593","DOIUrl":"https://doi.org/10.1002/cpdd.1593","url":null,"abstract":"<p><p>This 2-part, randomized, placebo-controlled, double-blind, Phase 1 study analyzed the pharmacokinetics, safety, and biomarker profile of fezolinetant in healthy Japanese individuals. Part 1: male participants received single doses of placebo or fezolinetant 15 or 60 mg. Part 2: male and premenopausal and postmenopausal female participants received a single dose of placebo or fezolinetant 180 mg, followed by a 2-day washout, and multiple dosing once daily for 10 days. Fezolinetant was rapidly absorbed with peak concentrations 1-2 hours after single-dose administration; plasma levels subsequently declined (half-life range, 3.29-7.24 hours). Only slight accumulation (area under the concentration-time curve accumulation ratio, 1.46‒1.57) was observed after once-daily multiple-dose administration. No serious/severe treatment-emergent adverse events were observed; the only fezolinetant-related treatment-emergent adverse event was mild uterine bleeding in 1 premenopausal woman and 1 postmenopausal woman. Concentration-QT analysis showed that fezolinetant does not have a clinically significant effect on QT interval. Fezolinetant produced dose-dependent reductions in luteinizing hormone and slight reductions in follicle-stimulating hormone; levels subsequently returned to baseline 48 hours or fewer after dosing. This analysis shows that fezolinetant doses up to 180 mg had an acceptable safety, pharmacokinetic, and biomarker profile. This study clarifies the safety, pharmacokinetic, and biomarker profiles of fezolinetant in Japanese individuals.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052105","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}

{"title":"Comparison of the Pharmacokinetics of Three Budesonide Formulations in Healthy Chinese Subjects.","authors":"Tengrui Yin, Jing Zou, Mei Tang, Mengchang Yang, Qiwen Han, Hao Jiang, Huihui Hu, Xiuyang Li, Yijue Wu, Yuanyuan Huang, Lin He","doi":"10.1002/cpdd.1603","DOIUrl":"https://doi.org/10.1002/cpdd.1603","url":null,"abstract":"<p><p>HR19042 is a novel, orally administered, targeted-release formulation of the topically active corticosteroid budesonide, developed to release active drug within the terminal ileum and indicated to reduced estimated glomerular filtration rate loss in adults with primary immunoglobulin A nephropathy. This randomized, single-dose, open-label, six-sequence, three-treatment crossover trial aimed to explore the pharmacokinetic (PK) of HR19042 in comparison with two other budesonide targeted-release formulations among healthy Chinese subjects. Plasma budesonide concentrations were measured via liquid chromatography with tandem mass spectrometry, and PK parameters were analyzed using non-compartmental methods. Eighteen subjects successfully completed the trial. The median T_lag and T_max of HR19042 were 1.25 and 3.50 h shorter than those of Nefecon, respectively. The C_max of HR19042 was approximately 1.9-fold higher than that of Nefecon and 1.4-fold higher than that of Budenofalk. Based on the AUC_0-t determination, the relative bioavailability (F) of HR19042 was approximately 136.93% relative to Nefecon and 129.68% relative to Budenofalk. In vitro, the dissolution of HR19042 occurred 30 min earlier than that of Nefecon in the intestinal buffer medium. In conclusion, both in vivo and in vitro findings suggest that HR19042 exhibits a faster absorption rate and higher oral bioavailability.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039283","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}

{"title":"Safety, Tolerability, and Pharmacokinetics of Galcanezumab, an Anti-CGRP Antibody, in Healthy Chinese Participants.","authors":"Jingjing Wang, Nanyang Li, Jinjie He, Jing Zhang, Lili Wang, William Kielbasa, Chenxi Qian, Yanjie Zhang, Liang Wang","doi":"10.1002/cpdd.1599","DOIUrl":"https://doi.org/10.1002/cpdd.1599","url":null,"abstract":"<p><p>Galcanezumab is used in several regions, including the United States, Europe, and China, as a preventive treatment for migraine. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PK) of galcanezumab in healthy Chinese participants. In this phase I single-dose study, 30 healthy adults were assigned to one of the two cohorts (120 or 240 mg) and randomized in a 4:1 ratio to receive a single subcutaneous (SC) dose of galcanezumab or placebo. Overall, 29 (96.7%) participants reported 93 treatment-emergent adverse events (TEAEs), with 21 participants reporting 44 TEAEs related to the study treatment. Most study-related TEAEs (95%) were mild in severity. The most commonly reported TEAE was upper respiratory tract infection. The PK data demonstrated that maximum observed drug concentration (C_max) and area under the serum concentration curve from time zero to infinity increased proportionally to dose, with an apparent clearance of 0.009 L/h and a terminal elimination half-life (t_1/2) of 27 days. Galcanezumab was safe and well tolerated and demonstrated a PK profile consistent with that of non-Chinese populations, supporting its use for the preventive treatment of migraine in Chinese patients.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052179","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}

{"title":"Pharmacokinetics and Bioequivalence of Two Formulations of Valsartan and Amlodipine Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.","authors":"Yu-Ying Xu, Wen-Tan Xu, Wei-Ping Pan, Xie-Li Guo, Xiao-Min Li, Su-Mei Xu, Shao-Wei Yan, Wen-Ke Cai, Xin-Bin Yan, Wen-Jing Zhong, Shi-Lin Chen, Ping-Sheng Xu","doi":"10.1002/cpdd.1597","DOIUrl":"https://doi.org/10.1002/cpdd.1597","url":null,"abstract":"<p><p>This study assessed the pharmacokinetics (PK) and bioequivalence (BE) of valsartan and amlodipine (80/5 mg) tablets in healthy Chinese subjects under fasting and fed conditions. A randomized, open-label, four-period crossover trial was conducted, with participants receiving test (T) or reference (R) formulations in cycles separated by a 14-day washout. Plasma concentrations of valsartan and amlodipine were measured using high-performance liquid chromatography-tandem mass spectrometry. PK parameters were analyzed noncompartmentally, and BE was evaluated using reference-scaled average bioequivalence (RSABE) for high-variability parameters (CV_W ≥ 30%) and average bioequivalence (ABE) for low-variability parameters (CV_W < 30%). Under fasting conditions, the maximum concentration of drug in blood plasma (C_max) of valsartan was assessed using RSABE methodology and demonstrated bioequivalence. For amlodipine, bioequivalence was established through conventional ABE analysis, with the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of C_max, AUC_0-t, and AUC_0-∞ all residing within the predefined equivalence boundaries. Under postprandial conditions, both drugs met BE criteria using ABE, with 90% CIs of GMRs within the acceptable range. Importantly, postprandial administration resulted in a significant reduction of approximately 30% in systemic exposure of valsartan for both test and reference formulations. All adverse events were mild and transient. The T and R formulations demonstrated bioequivalence and were well tolerated, supporting their interchangeability.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039242","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}