Clinical Pharmacology in Drug Development最新文献

{"title":"Pharmacokinetics and Bioequivalence of Tamsulosin Hydrochloride Extended-Release Capsules in Healthy Chinese Volunteers: A Randomized, Open-Label, Crossover Study Under Fasting and Fed Conditions","authors":"Lijie Du,&nbsp;Xiaolu Wang,&nbsp;Yi Zhang,&nbsp;Jiamin Yang,&nbsp;Fangliang Gan,&nbsp;Yaxun Pang","doi":"10.1002/cpdd.70078","DOIUrl":"10.1002/cpdd.70078","url":null,"abstract":"<p>Tamsulosin hydrochloride is a long-acting, highly selective α1A receptor antagonist, primarily used to treat benign prostatic hyperplasia. It effectively alleviates lower urinary tract symptoms, including dysuria, nocturia, and urgency caused by prostate enlargement. This study aimed to evaluate the pharmacokinetics and bioequivalence of two tamsulosin extended-release capsules in Chinese volunteers under both fasting and fed conditions. A single-center, randomized, open-label, two-formulation, single-dose, two-period, two-way crossover design was used. A total of 64 healthy volunteers were enrolled, with 28 in the fasting group and 36 in the fed group. In the fasting group, each subject received a single dose of either the test or reference formulation in a randomized crossover design. In the fed group, volunteers consumed a high-fat meal 1 h before dosing. Blood samples were collected for up to 72 h post-dose, and plasma tamsulosin concentrations were measured using liquid chromatography-tandem mass spectrometry. The geometric mean ratios and 90% confidence intervals for key exposure metrics for both formulations under fasting and fed conditions were within the 0.8000-1.2500 bioequivalence range. Both formulations demonstrated bioequivalence under both conditions, and no severe adverse events were observed.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 7","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520013","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 ABBV-552 Safety and Pharmacokinetics in Healthy Asian and Western Adults","authors":"Nick Miles,&nbsp;Brian McNamee,&nbsp;Cindy Zadikoff,&nbsp;Joey Boiser,&nbsp;Mohamad Shebley,&nbsp;Ramesh Boinpally","doi":"10.1002/cpdd.70072","DOIUrl":"https://doi.org/10.1002/cpdd.70072","url":null,"abstract":"<p>ABBV-552, a positive modulator of synaptic vesicle glycoprotein 2A (SV2A), was under investigation as a treatment for cognitive impairment related to Alzheimer's disease. This Phase 1, multicenter, open-label, parallel cohort study (NCT05686980) was conducted to examine the pharmacokinetics (PK), safety, and tolerability of ABBV-552 in healthy adult Japanese and Han Chinese participants and to compare PK and safety findings with healthy adult Western participants from previous studies. Japanese participants in Cohort 1 (N = 10) received three ascending single oral doses (5, 15, and 40 mg) of ABBV-552 with a washout of 7 days between doses. Han Chinese participants in Cohort 2 (N = 7) received a single oral dose of 40 mg ABBV-552. After a single oral dose of 40 mg ABBV-552, PK was comparable between both cohorts. Additionally, the range of individual ABBV-552 concentrations and mean 24-h profiles were comparable with historical data in healthy adult Western participants. In this small study population, single doses of ABBV-552 were well tolerated at all tested doses. Common adverse events reported were dizziness (39%), somnolence (11%), and fatigue (11%). No unique safety signals following single dose ABBV-552 administration were observed in the Japanese or Han Chinese populations examined compared with the previously examined Western population.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 7","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358099","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":"Beyond the “Undruggable”: What Pancreatic Cancer Teaches Us About the Next Evolution of Clinical Pharmacology","authors":"Amalia M. Issa PhD, MPH","doi":"10.1002/cpdd.70079","DOIUrl":"https://doi.org/10.1002/cpdd.70079","url":null,"abstract":"&lt;p&gt;Recent reports of the pan-RAS inhibitor daraxonrasib producing substantial improvements in overall survival among patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) have generated unusual enthusiasm within the oncology community.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; In the Phase III RASolute 302 study, median overall survival reportedly increased from approximately 6.7 months with standard chemotherapy to 13.2 months with daraxonrasib, a result many investigators have characterized as one of the most significant advances in pancreatic cancer treatment in decades. While not a cure, and while resistance mechanisms will undoubtedly emerge, the finding represents something more important than a successful drug. It represents the culmination of a decades-long scientific journey from a seemingly biological impossibility to therapeutic reality.&lt;/p&gt;&lt;p&gt;The timeline of KRAS-directed drug development is instructive. KRAS mutations were first identified in human cancers in the early 1980s and recognized as a central driver of pancreatic cancer. Yet for much of the past four decades, KRAS was considered “undruggable”.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; It is only recently that meaningful therapeutic interventions have started to become possible. During this interval, advances in structural biology enabled visualization of previously inaccessible binding pockets.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Medicinal chemistry generated compounds capable of exploiting these vulnerabilities. Biomarker technologies improved patient selection. Computational methods expanded our understanding of signaling networks and resistance pathways. Clinical trial methodologies evolved to accommodate molecularly defined populations.&lt;/p&gt;&lt;p&gt;The lesson is not merely that scientific persistence eventually succeeded. Rather, it is that the conventional architecture of drug development was too slow, too fragmented, and too sequential for the biological complexity it sought to address. Importantly, no single innovation solved the problem. Instead, success emerged from the accumulation and integration of advances across multiple disciplines. The therapeutic breakthrough followed the maturation of an ecosystem. This observation has implications that extend well beyond pancreatic cancer.&lt;/p&gt;&lt;p&gt;Many diseases that remain without effective therapies today, including various neurodegenerative disorders, fibrotic diseases, rare genetic conditions, and numerous solid tumors, share characteristics with pancreatic cancer. Their biology is complex. Disease progression is heterogeneous. Therapeutic response evolves dynamically. Conventional development pathways frequently struggle to accommodate this complexity.&lt;/p&gt;&lt;p&gt;Recent discussions within the clinical pharmacology community have emphasized the transformative potential of artificial intelligence, quantitative systems pharmacology, model-informed drug development, advanced biomarkers, and real-world evidence.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; These d","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 7","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358100","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":"Bioequivalence of a Fixed-Dose Combination of Relugolix, Estradiol, and Norethindrone Acetate: An Open-Label, Randomized, Fully Replicate Crossover Study in Healthy Postmenopausal Women Under Fasting Conditions","authors":"Ravi Kotadia,&nbsp;Sudershan Kumar,&nbsp;Arshad Khuroo,&nbsp;Shruti Dharmadhikari,&nbsp;Pradeep Shahi,&nbsp;Goru N. V. S. Satya Narayana,&nbsp;Simrit Reyar","doi":"10.1002/cpdd.70076","DOIUrl":"10.1002/cpdd.70076","url":null,"abstract":"<p>Uterine fibroids are the most common benign gynecological tumors, often causing heavy menstrual bleeding (HMB), anemia, and impaired quality of life. A fixed-dose combination (FDC) of relugolix (40 mg), estradiol (1 mg), and norethindrone acetate (0.5 mg) was developed to address these limitations. This open-label, randomized, two-treatment, two-sequence, four-period, crossover bioequivalence study was conducted in 48 healthy postmenopausal women under fasting conditions. Participants received a single oral dose of either the RELUEASE (Sun Pharmaceutical Industries Limited, India) or the reference product (MYFEMBREE) (Patheon Inc., Mississauga, Ontario), with a 21-day washout. Pharmacokinetics parameters were derived using non-compartmental analysis. Bioequivalence assessment was performed using a linear mixed-effects model applied to ln-transformed pharmacokinetic parameters. A total of 39 participants completed all study periods. The point estimates and 90% confidence intervals (CIs), or the 95% upper bound for the pharmacokinetic parameters (C_max and AUC) of relugolix, estradiol, norethindrone, and estrone met the predefined bioequivalence acceptance criteria. Six adverse events were reported, all mild, transient in nature, and resolving without sequelae. No clinically significant safety concerns were observed during the study. The relugolix/estradiol/norethindrone acetate FDC demonstrated bioequivalence to the globally approved reference product (MYFEMBREE) with comparable tolerability. This provides a safe, effective, reversible non-surgical therapy for fibroid-related HMB, fulfilling an unmet need beyond surgery.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276374","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":"A Phase 1 Study to Assess the Relative Bioavailability of Brigatinib Administered as an Oral Solution Versus an Immediate-Release Tablet in Healthy Adults","authors":"Michael J. Hanley,&nbsp;Ronald Gounden,&nbsp;Bradley Hupf,&nbsp;Saurabh Sarkar,&nbsp;Robert J. Fram,&nbsp;Neeraj Gupta","doi":"10.1002/cpdd.70075","DOIUrl":"10.1002/cpdd.70075","url":null,"abstract":"<p>Brigatinib is an ALK tyrosine kinase inhibitor approved for the treatment of adults with <i>ALK</i>+ non-small cell lung cancer. The commercial formulation of brigatinib is an immediate-release (IR) tablet; however, an oral solution was developed for use in pediatric studies for patients unable to swallow solid oral dosage forms. This randomized, two-period, two-sequence crossover study assessed the relative bioavailability of the oral solution versus the IR tablet in healthy adults. Twelve participants received a single 90-mg brigatinib dose as the oral solution or IR tablet on Day 1 of the first study period, followed by the alternate formulation on Day 1 of the second study period. Brigatinib pharmacokinetic parameters were similar following administration of the oral solution and IR tablet. The geometric least-square mean ratios (oral solution vs IR tablet) for C_max (0.92), AUC_last (0.96), and AUC_inf (0.96) were close to 1.00 with 90% confidence intervals within the bioequivalence range of 0.80–1.25 (C_max, 0.87–0.98; AUC_last, 0.88–1.04; AUC_inf, 0.89–1.03). Treatment-emergent adverse events were reported in three participants (25%), with the most frequent being cough (17%). These results indicate that the oral solution and IR tablet can be used interchangeably without dose adjustment in pediatric studies.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249542","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":"Effect of High-Fat Meal on the Pharmacokinetics and Safety of Lansoprazole Enteric-Coated Capsules in Healthy Chinese Subjects","authors":"Yifei Wang,&nbsp;Xiaojing Huang,&nbsp;Dandan Han,&nbsp;Liguang Duan,&nbsp;Qinchao Wang,&nbsp;Zihuan Zhang,&nbsp;Mingyue Liu,&nbsp;Linliu Du,&nbsp;Jianxin Wang","doi":"10.1002/cpdd.70069","DOIUrl":"10.1002/cpdd.70069","url":null,"abstract":"<p>The effects of food on the pharmacokinetics (PKs) and safety of 30-mg lansoprazole enteric-coated capsules in healthy Chinese subjects were investigated from a bioequivalence trial. A randomized, open-label, four-period crossover study was conducted in 73 healthy subjects under both fasted and fed conditions. Serial blood samples were collected, and plasma lansoprazole concentrations were determined by liquid chromatography-tandem mass spectrometry. PK parameters were calculated using a non-compartmental model with Phoenix WinNonlin Version 8.3 software. The bioequivalence module of WinNonLin was used to statistically analyze the maximum plasma concentration (C_max), the area under the concentration–time curve from zero to the last measurable concentration (AUC_0-t), and the area under the concentration–time curve from zero to infinity (AUC_0-∞) of lansoprazole in plasma. The results demonstrated bioequivalence between the test (T) and reference (R) formulations for all evaluated PK parameters. Compared with the fasted state, the C_max, AUC_0-t, and AUC_0-∞ of lansoprazole significantly decreased by 60.67%, 46.39%, and 44.25%, respectively, following oral administration of lansoprazole 30 mg in the fed state. The incidence of adverse events (AEs) was similar between the fasted and fed states, with no serious AEs observed. Overall, food markedly reduced systemic exposure of 30 mg oral lansoprazole in Chinese subjects, indicating that food intake significantly affects its bioavailability.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154968","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":"Population Pharmacokinetic-Based Meropenem Dosing in Critically and Non-Critically Ill Patients with Mixed Gram-Negative Bacterial Infections","authors":"Shuo Shi,&nbsp;Jie Cui,&nbsp;Guangqing Liu,&nbsp;Jin Gao,&nbsp;Wanjun Bai","doi":"10.1002/cpdd.70067","DOIUrl":"10.1002/cpdd.70067","url":null,"abstract":"<p>This study aimed to describe the population pharmacokinetic (PK) of meropenem in patients with mixed Gram-negative bacterial infections, and further to develop optimal dosing regimens for both non-critically ill and critically ill patients by combining different pharmacokinetic/pharmacodynamic (PK/PD) targets. Based on retrospectively collected data from patients who underwent therapeutic drug monitoring (TDM) for meropenem, including demographic characteristics, medication records, and laboratory results, a population PK model was developed via nonlinear mixed-effects modeling. Dosing regimens were subsequently evaluated and provided through Monte Carlo simulation. The population PK analysis of meropenem included 86 steady-state concentrations from 39 adult patients. The data were modeled using a one-compartment model. The final model yielded a population typical value for clearance (CL) of 6.10 L/h. Our study showed that estimated glomerular filtration rate (eGFR) significantly affected the PK of meropenem. Monte Carlo simulation results demonstrated that a regimen of 0.5-h infusion every 8 h was sufficient to achieve the conventional target of 40% <i>ƒ</i>T &gt; MIC in most scenarios. In contrast, achieving the more aggressive target of 100% ƒT &gt; MIC required a regimen of every 6 h; for MIC ≥ 4 mg/L pathogens, this needed to be coupled with an extended infusion time of 3 h. Furthermore, continuous infusion regimens demonstrated a distinct advantage in critically ill patients. This study successfully established a population PK model of meropenem and provided a reference for dosing adjustment based on clinical severity and renal function.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161835","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":"Scientific Fraud: How Do We Ensure Sound Medical Literature?","authors":"Michael J. Fossler,&nbsp;Katy P. Moore","doi":"10.1002/cpdd.70068","DOIUrl":"10.1002/cpdd.70068","url":null,"abstract":"&lt;p&gt;There have been some recent disturbing reports of scientific fraud over the past few decades, and the news is reaching the lay press.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The impact of fraudulent science goes far beyond the actual crime itself, although that is worrisome enough. Scientific fraud erodes the trust the public has in science and its practitioners. Even more concerning for clinical practitioners and researchers is the perpetuation of disinformation and contrived data poisoning of large language models (LLMs) and artificial intelligence (AI) outputs. Recently, to test AI, scientists intentionally invented a fake disease with a fake researcher and fake data in publications that included obvious clues the paper was suspect, such as a non-existent researcher (including a photo of the researcher generated from AI) and a non-existent university.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The impact of certain scientific challenges and communication issues during the COVID-19 pandemic has shaken the public's faith in the scientific community, the pharmaceutical industry, and global public health systems. Continued instances of scientific fraud and lack of action by the scientific community to combat it will have damaging effects on public health.&lt;/p&gt;&lt;p&gt;Sadly, scientific fraud has been with us for a long time. Gregor Mendel's celebrated work in pea plant genetics was, while not completely fraudulent, almost certainly “touched up” by the monk.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The “discovery” of the Piltdown man fossil in 1912 (which was exposed as a forged, manufactured “fossil” in 1953) was accepted for decades and had a significantly negative impact on anthropology.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; These incidents in the natural sciences are treated as anomalies for the most part, and although damaging to the reputation of scientists and a substantial waste of resources to discover and correct the error, they have probably done little lasting harm over the span of time and persistence of validation in scientific discovery.&lt;/p&gt;&lt;p&gt;Scientific fraud in medicine has a much more insidious impact on society. The fraudulent work of Andrew Wakefield, who claimed to have found a link between the MMR vaccine and autism, continues to fuel mistrust in vaccines to this day, even though he was stripped of his medical license and both of his papers were retracted.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; The continued mistrust of vaccines resulting from this fraudulent work by laypeople and even some in government may have contributed to an increase in the cases of childhood diseases, which were thought to be almost eradicated.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Papers on Alzheimer's disease produced by a prominent Stanford researcher were later found to contain manipulated images. Although the papers were later withdrawn, it took nearly a decade for this to happen&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; and resulted in a huge amount of wasted effort and time on the part of other researchers.&lt;/p&gt;&lt;p&gt;More recently, the Dana-Farber Cancer Ins","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136876","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":"Comparative Pharmacokinetics of Two Extended-Release Tablet Formulations of Upadacitinib: Bioequivalence Assessment","authors":"Biao Sun,&nbsp;Li Zhao,&nbsp;Fangliang Gan,&nbsp;Qiong Zhan","doi":"10.1002/cpdd.70073","DOIUrl":"10.1002/cpdd.70073","url":null,"abstract":"<p>The aim of this study is to evaluate the pharmacokinetic characteristics, bioequivalence, and safety of two brands of upadacitinib (UPA) extended-release tablets (15 mg) in healthy Chinese subjects under fasting and postprandial conditions. The plasma concentration of UPA was determined by ultra-high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated using a non-compartmental model (NCA module) with Phoenix WinNonlin 8.2 (Certara, USA) software, followed by bioequivalence evaluation. The results demonstrate that the 90% confidence intervals for the geometric least-squares mean ratios of C_max, AUC_0–t, and AUC_0–∞ between the test and reference formulations fall within the range of 0.80−1.25, indicating that both formulations are bioequivalent in terms of absorption rate and extent under fasting and postprandial conditions. No serious adverse events occurred, and observed drug-related adverse events were mild under both conditions, indicating comparable safety of the two formulations.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053120","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 Tolerability of Entacapone, Levodopa, and Carbidopa Tablets in Healthy Chinese Subjects: A Randomized, Open-Label, Four-Period Crossover Study Under Fasting and Fed Conditions","authors":"Jingyan Wang,&nbsp;Yuan Xu,&nbsp;Ye Tao,&nbsp;Xuewei Ma,&nbsp;Yang Zou,&nbsp;Zhen Yang,&nbsp;Yi Lan","doi":"10.1002/cpdd.70071","DOIUrl":"10.1002/cpdd.70071","url":null,"abstract":"<p>This study aimed to assess the pharmacokinetics, bioequivalence, and safety of a generic entacapone/levodopa/carbidopa (100/25/200 mg) tablet formulation compared to its reference listed drug (RLD, Stalevo) in healthy Chinese adults. A randomized, open-label, single-dose, four-period crossover study was conducted under fasting and fed conditions, with a 5-day washout. A total of 68 subjects were enrolled and randomly assigned (1:1) to receive a single oral dose of either the test or reference formulation. Plasma concentrations of analytes were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and key pharmacokinetic parameters (C_max, AUC_0–t, AUC_0–∞) were calculated. Under both fasting and fed conditions, bioequivalence was assessed under both fasting and fed conditions using the reference-scaled average bioequivalence (RSABE) or average bioequivalence (ABE) approach. For the key pharmacokinetic parameters (C_max, AUC_0–t, and AUC_0–∞), the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) all fell within the 80.00%–125.00% range, or the one-sided 95% upper confidence bound for the scaled difference was ≤0 and the point estimate of the GMR between the test and reference formulations fell within the 80.00%–125.00% range, thus confirming bioequivalence. Concomitant high-fat food intake had a certain impact on the pharmacokinetics of each active ingredient. Adverse events (AEs) were mild, with no serious AEs reported, indicating comparable safety profiles. In conclusion, the generic formulation is bioequivalent to the RLD and demonstrates an acceptable safety profile in healthy Chinese subjects.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053147","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}