Clinical Pharmacology in Drug Development最新文献

{"title":"Integrating Pharmacogenomic Insights in GLP-1 Receptor Agonist Therapy: Direct GLP1R and ARRB1 Variants and Indirect CYP2D6 Influences in Personalized Obesity Management","authors":"Navodi Sandamini Jayathilaka,&nbsp;Arunodya Vishwanthi Weththasinghe,&nbsp;Nila Ganamurali,&nbsp;Sarvesh Sabarathinam","doi":"10.1002/cpdd.1624","DOIUrl":"10.1002/cpdd.1624","url":null,"abstract":"<p>Glucagon-like peptide-1 (GLP-1) receptor agonists have become frontline agents in obesity treatment due to their efficacy. However, there is considerable inter-individual variability in treatment response. Although these agents are primarily degraded by proteolytic enzymes rather than cytochrome P450 (CYP) pathways, pharmacogenomic factors may indirectly influence therapeutic outcomes. This review investigates the role of CYP2D6 polymorphisms in optimizing GLP-1 receptor agonist therapy in obesity. It explores genetic influences on treatment variability and highlights the importance of personalized dosing strategies. A systematic search of PubMed, Embase, and Web of Science (1990-2025) was conducted using terms such as “CYP2D6 polymorphisms,” “GLP-1 receptor agonists,” “pharmacogenomics,” and “personalized medicine.” Emphasis was placed on primary experimental studies. While GLP-1RAs are not CYP2D6 substrates, pharmacogenomic factors play a key role through indirect mechanisms. ARRB1 (rs140226575 and Thr370Met) and GLP1R (rs6923761 and Gly168Ser) variants affect glycemic response. CYP2D6 polymorphisms significantly influence metabolism of concomitant medications (e.g., antidepressants and beta-blockers), affecting efficacy and safety. Ethnic variability in CYP2D6 allele frequencies further underscores the need for tailored approaches. Integrating pharmacogenomic data, including CYP2D6 status, can support personalized obesity management and improve clinical outcomes. The primary metabolizers of GLP-1 receptor agonists are proteolytic enzymes; nevertheless, pharmacogenomic heterogeneity influences treatment results via both direct and indirect mechanisms. Variants in CYP2D6 polymorphisms have an indirect impact on treatment outcomes through changed metabolism of concurrent drugs including beta-blockers and antidepressants, while variations in GLP1R and ARRB1 directly affect receptor signaling and weight loss effectiveness.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522661","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":"Pharmacokinetic Comparison Between a Fixed-Dose Combination of Atorvastatin/Fenofibrate 20/145 mg and the Corresponding Individual Components","authors":"Seungri Lee,&nbsp;Juyoung Khwarg,&nbsp;Sungyeun Bae,&nbsp;Dong-Min Park,&nbsp;Heejung Park,&nbsp;SeungHwan Lee,&nbsp;Kyung-Sang Yu","doi":"10.1002/cpdd.70043","DOIUrl":"10.1002/cpdd.70043","url":null,"abstract":"<p>Co-administration of atorvastatin and fenofibrate has demonstrated clinical benefits in patients with dyslipidemia. To improve convenience and adherence, a fixed-dose combination (FDC) of the two agents has gained interest. This study aimed to compare the pharmacokinetics (PKs) and safety of an FDC of atorvastatin/fenofibrate 20/145 mg with the corresponding individual components. A randomized, open-label, single-dose, two-sequence, two-treatment, four-period full replicated crossover study was conducted. Participants were randomly assigned to one of the two sequences and received FDC or individual components. PK parameters were estimated using a non-compartmental method. The geometric mean ratio (GMR) and its 90% confidence interval (CI) of the FDC to the individual components were calculated using mixed effect model. A total of 36 participants completed the study. The GMRs (90% CIs) for maximum plasma concentration and area under the time-concentration curve from zero to the last measurable point were 1.1038 (0.9985-1.2202) and 1.0148 (0.9745–1.0567) for atorvastatin, 1.0032 (0.9261-1.0867) and 0.9882 (0.9520–1.0258) for 2-OH atorvastatin. For fenofibric acid, the corresponding values were 0.9896 (0.8810-1.1116) and 0.9871 (0.8869-1.0986), respectively. The FDC of atorvastatin/fenofibrate 20/145 mg showed comparable PK profiles to the corresponding individual components, supporting its potential as an alternative therapeutic option for dyslipidemia with convenience.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389734","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 Study of Two Olopatadine Hydrochloride Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions","authors":"Yuyan Lei,&nbsp;Fang Pei,&nbsp;Qingqi Wu,&nbsp;Guiling Xiong,&nbsp;Fengzhi Liu,&nbsp;Xintong Wang,&nbsp;Lulu Chen,&nbsp;Chao Li,&nbsp;Ling Zhou,&nbsp;Qing Fang,&nbsp;Weiming Chen,&nbsp;Dongsheng Ouyang,&nbsp;Xiaohui Li","doi":"10.1002/cpdd.1629","DOIUrl":"10.1002/cpdd.1629","url":null,"abstract":"<p>Olopatadine hydrochloride, a second-generation selective histamine H1 receptor antagonist, is an effective anti-allergic agent. This study evaluated the pharmacokinetics and bioequivalence of two olopatadine hydrochloride tablet formulations in healthy Chinese subjects under fasting (n = 24) and fed (n = 24) conditions. A single-center, randomized, open-label, single-dose, two-way crossover study was conducted, in which 48 subjects were randomized to receive 5 mg of the test or reference formulation, followed by a 7-day washout period. Blood samples were collected at predefined intervals up to 24 h post-dose, and olopatadine plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. The results demonstrated no significant differences in the pharmacokinetic profiles between the test and reference formulations under fasting or fed conditions. The 90% confidence intervals (CIs) for the ratio of geometric means of C_max, AUC_0–t, and AUC_0–∞ of olopatadine hydrochloride under both conditions were within the bioequivalence range of 0.80–1.25. A high-fat diet delayed olopatadine hydrochloride absorption, leading to a reduction in C_max to approximately 60% of the fasting value and a decrease in AUC to 85%–90%. No serious adverse events occurred, and safety profiles were comparable between formulations. This research confirmed the bioequivalence and similar safety of the generic olopatadine hydrochloride tablets to the reference formulation.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548577","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":"Results of a Phase 1 Study Assessing the Effect of CIN-102, a Novel Formulation of the Dopamine Receptor Antagonist Domperidone Designed to Treat Gastroparesis, on Cardiac Repolarization in Healthy Volunteers","authors":"Mary Bond,&nbsp;Brian Murphy,&nbsp;Brendan Doran,&nbsp;Borje Darpo,&nbsp;Hongqi Xue,&nbsp;Leela Vrishabhendra,&nbsp;Jon Isaacsohn","doi":"10.1002/cpdd.70039","DOIUrl":"10.1002/cpdd.70039","url":null,"abstract":"<p>CIN-102 is a deuterated form of domperidone in development for the treatment of acute, recurrent gastroparesis. This thorough QT study assessed the effects of CIN-102 on cardiac repolarization in 62 healthy volunteers. In this 4-period randomized crossover study, participants were administered single doses of 30-mg CIN-102 (representing therapeutic exposures), 100-mg CIN-102 (representing supratherapeutic exposures), placebo, and moxifloxacin (positive control). Continuous 12-lead electrocardiograms (ECGs) and time-matched blood samples were collected to determine plasma levels of deuterated domperidone and its major metabolites. The primary endpoint was placebo-corrected change-from-baseline QTc corrected by Fridericia's formula (ΔΔQTcF). By-time-point and concentration-QTc analyses excluded an effect on ΔΔQTcF exceeding 10 ms for both doses of CIN-102 at all time points up to deuterated domperidone plasma concentrations of ≈92  ng/mL (≈6 times the therapeutic steady-state concentration). There were no clinically relevant effects of CIN-102 on heart rate or cardiac conduction, and no deaths or serious adverse events occurred. This thorough QT study demonstrated that at doses producing therapeutic and supratherapeutic exposures, CIN-102 does not have a clinically meaningful effect on ECG parameters, including QT interval. This modified formulation of domperidone provides a potential gastroparesis treatment while decreasing the risk of QT prolongation associated with the traditional formulation of domperidone.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12969247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375933","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 Randomized, Double-Blind, Two-Treatment, Two-Period, Crossover Study Investigating the Systemic Bioavailability of a Novel Cocrystal Ubiquinol Formulation Compared with a Ubiquinone Formulation in Healthy Adults","authors":"Xuefeng Mei,&nbsp;Bingqing Zhu,&nbsp;Kshitij Soni,&nbsp;Kishore Kasaraneni,&nbsp;Nirav Panchal","doi":"10.1002/cpdd.70042","DOIUrl":"10.1002/cpdd.70042","url":null,"abstract":"<p>Coenzyme Q10 (CoQ10) is a naturally occurring biochemical cofactor found in all human cell membranes in two interconvertible forms: oxidized ubiquinone and reduced ubiquinol. Clinical studies indicate that different CoQ10 formulations have different absorption rates, highlighting research comparing their systemic bioavailability. This study compared the oral bioavailability of cocrystal formulation soft gels (test product), a novel ubiquinol formulation, and ubiquinone formulation (reference product) in a randomized, double-blind, two-period crossover study with 12 healthy subjects under fasting conditions. The secondary objective of this study was to evaluate the safety and tolerability of the ubiquinol formulation. The pharmacokinetic analyses indicated that the test ubiquinol formulation demonstrated substantially higher relative systemic bioavailability compared with the ubiquinone reference. The geometric mean ratios (test/reference) for baseline-corrected peak plasma concentration (C_max) and area under the curve from zero to last quantifiable time (AUC_0–t) were 2.20 and 2.01, respectively, with 90% confidence intervals of 1.59–3.04 and 1.51–2.70. The geometric mean ratio for AUC from time zero to infinity (AUC_0–∞) was 3.43 (90% CI: 1.47–8.00). No adverse events were reported in this small pilot study for either of the formulations. These findings demonstrate that ubiquinol has a better systemic bioavailability than ubiquinone, supporting the novel formulation's potential as a promising alternative to traditional CoQ10 supplements.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147363644","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":"Absolute Bioavailability and Absorption, Distribution, Metabolism, and Excretion of [14C]Xevinapant, a Potent, Oral, Small-Molecule IAP Inhibitor","authors":"Annick Menetrey,&nbsp;Valérie Nicolas-Metral,&nbsp;Marie-Claude Roubaudi-Fraschini,&nbsp;Tri Tat,&nbsp;Yuan Zhao,&nbsp;Yulia Vugmeyster,&nbsp;Karthik Venkatakrishnan,&nbsp;Felix Rohdich,&nbsp;Holger Scheible","doi":"10.1002/cpdd.70028","DOIUrl":"10.1002/cpdd.70028","url":null,"abstract":"<p>This Phase 1, open-label, 2-part, single-dose study aimed to investigate the pharmacokinetics, metabolism, and excretion of xevinapant, a small molecule inhibitor of apoptosis proteins (IAPs), in healthy male subjects. Part 1 focused on determining the mass balance recovery, pharmacokinetics, and metabolic profile of [¹⁴C]xevinapant following a single oral dose of 200 mg. Part 2 aimed to determine the absolute oral bioavailability of xevinapant by evaluating the pharmacokinetics of an oral dose of 200 mg xevinapant in comparison to an intravenous microtracer dose of [¹⁴C]xevinapant using accelerator mass spectrometry. After oral administration, xevinapant was rapidly absorbed, with a median time to maximum concentration of 0.5 h and a geometric mean half-life of 13.2 h. The principal route of excretion of drug-related material was fecal, accounting for 60.2% of the administered dose, while 33.3% was excreted in urine. Renal clearance accounted for 18.4% of total clearance. In addition to xevinapant, seven metabolites were structurally characterized in the samples analyzed. The principal route of metabolism was dealkylation to form metabolite D-1143-MET1, with secondary metabolism by oxidation. The major circulating components in plasma were xevinapant and D-1143-MET1 (inactive on IAPs), which represented 28% and 42% of the total drug-related exposure, respectively. The absolute oral bioavailability of xevinapant was determined to be 57.8%. The clearance of [¹⁴C]xevinapant was 12.2 L/h and the volume of distribution at steady-state was 75.3 L. Xevinapant was well tolerated in healthy male subjects, with no clinically significant findings in clinical laboratory evaluations, vital signs, ECG, or physical examinations.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354154","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":"The FDA Roadmap to Reducing Animal Testing in Preclinical Safety Studies: Where Will It Lead Us?","authors":"Michael J. Fossler,&nbsp;C. Edwin Garner","doi":"10.1002/cpdd.70046","DOIUrl":"10.1002/cpdd.70046","url":null,"abstract":"&lt;p&gt;For several years, the FDA, EMA, and other regulatory agencies have been concerned about the number of animals used in drug research, particularly regarding toxicology studies.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This concern is not only based on animal welfare considerations; it is also based on the understanding that animal toxicology data does not always accurately predict human toxicity.&lt;/p&gt;&lt;p&gt;Against this backdrop, in April 2025, the FDA published its Roadmap to reduce animal testing in preclinical safety studies.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The Roadmap outlines a comprehensive long-term plan to reduce or possibly eliminate animal toxicology testing, starting with monoclonal antibodies (mAbs), by using what are termed “New Approach Methodologies” (NAMs), which include the use of human tissue-based systems, such as organs-on-chips (OOCs)—human tissue constructs maintained in a microfluidic environment—&lt;i&gt;in silico&lt;/i&gt; modeling (physiologically based pharmacokinetics modeling [PBPK] and systems pharmacology modeling), and other innovative approaches, such as high-throughput cell-based screening.&lt;/p&gt;&lt;p&gt;As stated in the Roadmap, the goal (3–5 years from the date of publication of this Roadmap) is to make animal studies the exception, rather than the norm, not only for mAbs, but for all therapeutics. We question whether the complete elimination of all animal toxicology studies is a reasonable goal. It is important to remember that, while animal studies might not be perfect, they have been used in science for hundreds of years to very good effect. For the most part, preclinical toxicology studies do a good job of predicting human safety (i.e., absence of toxicological response), and this is why they have been required for decades.&lt;/p&gt;&lt;p&gt;The preclinical in vivo IND-enabling toxicity study program approach to assess the general toxicity of pharmaceuticals has been generally successful in allowing reasonably safe clinical trials to proceed.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; From 2000 to 2010, approximately 18% of all clinical programs were discontinued due to either animal or human toxicity (vs 20%–30% for the 50 years prior). In addition, the general ability of animal toxicity data to identify potential adverse human effects is good,&lt;span&gt;&lt;sup&gt;9, 10&lt;/sup&gt;&lt;/span&gt; and the absence of animal toxicity is particularly good at predicting an &lt;i&gt;absence of toxicities&lt;/i&gt; in human Phase 1 clinical trials.&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; That is, a greater than 86% effective rate for human safety of new chemical entities with unknown properties. However, the ability of animal studies to predict a specific &lt;i&gt;toxicity&lt;/i&gt; incidence is about 50%.&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;There are currently no alternative predictive toxicological methods that readily allow identification of appropriate dose ranges for clinical exploration and of potential adverse effects over time regarding systemic exposure. As such, there is a very low likelihood of replacing whole animal general toxicity stu","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://accp1.onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324808","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":"Pharmacokinetic and Bioequivalence Evaluation of Two Lercanidipine Hydrochloride Tablets in Healthy Chinese Volunteers","authors":"Biao Sun,&nbsp;Li Zhao,&nbsp;Fangliang Gan,&nbsp;Qiong Zhan","doi":"10.1002/cpdd.70045","DOIUrl":"10.1002/cpdd.70045","url":null,"abstract":"<p>Lercanidipine hydrochloride is a third-generation dihydropyridine calcium channel blocker used to treat mild-to-moderate hypertension. The aim of this study is to compare the pharmacokinetic characteristics of lercanidipine hydrochloride tablets (10 mg) in healthy Chinese volunteers after oral administration under fasting conditions with those of a reference formulation, and to evaluate the bioequivalence and safety of the two formulations. A validated liquid chromatography-tandem mass spectrometry method was established to determine the plasma concentration of lercanidipine. Phoenix WinNonlin software (version 7.0) was used to calculate pharmacokinetic parameters based on plasma drug concentration–time data. The geometric mean ratios and 90% confidence intervals of C_max, AUC_0–t, and AUC_0–∞ for the test formulation relative to the reference formulation were 110.37% (99.96%–121.86%), 106.81% (99.65%–114.49%), and 106.91% (99.86%–114.45%), respectively, all within the range of 80.00%–125.00%. The test formulation met the bioequivalence acceptance criteria and was well tolerated by healthy Chinese volunteers under fasting conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324789","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":"Pharmacokinetic and Bioequivalence Evaluation of Two Repaglinide Tablets Under Fasting and Fed Conditions in Healthy Chinese Volunteers","authors":"Biao Sun,&nbsp;Li Zhao,&nbsp;Fangliang Gan,&nbsp;Qiong Zhan","doi":"10.1002/cpdd.70044","DOIUrl":"10.1002/cpdd.70044","url":null,"abstract":"<p>Repaglinide, an insulin secretagogue that predominantly lowers postprandial glucose, is approved for patients with type 2 diabetes inadequately controlled by diet, weight loss, and exercise. This study used a single-center, randomized, open-label, two-formulation, single-dose, four-period, fully replicated, crossover design to evaluate the pharmacokinetics, bioequivalence, and safety of generic repaglinide tablets (1 mg) versus the innovator product in healthy Chinese subjects under fasting and fed conditions. Blood samples were assayed by validated liquid chromatography-tandem mass spectrometry. After natural logarithmic transformation of pharmacokinetic parameters (C_max, AUC_0–t, and AUC_0–∞), the bioequivalence of the test formulation and the reference formulation was evaluated using two one-sided t-tests and the 90% confidence intervals (CIs) method. The least-squares geometric mean ratios (test/reference) and 90% CIs for C_max, AUC_0–t, and AUC_0–∞ all fell within the conventional bioequivalence ranges of 0.80–1.25. Both formulations were well tolerated, with no serious adverse events reported, and the food effect on repaglinide pharmacokinetics is further discussed. In summary, test and reference repaglinide tablets are bioequivalent and demonstrate similar pharmacokinetic characteristics and safety in healthy Chinese volunteers under both fasting and fed states.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303026","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":"Pharmacokinetic Characterization and Bioequivalence of Sildenafil Citrate Orally Disintegrating Tablets in Healthy Volunteers","authors":"Yi Zhang,&nbsp;Lijie Du,&nbsp;Shirong Liu,&nbsp;Guiying Chen,&nbsp;Haoran Han,&nbsp;Jiangeng Huang,&nbsp;Hongliang Jiang,&nbsp;Xiaolu Wang,&nbsp;Dongsheng Guo,&nbsp;Fangliang Gan","doi":"10.1002/cpdd.70041","DOIUrl":"10.1002/cpdd.70041","url":null,"abstract":"<p>This study characterized the pharmacokinetic (PK) profile and evaluated the bioequivalence of sildenafil citrate under fasting conditions in Chinese subjects. A single-center, randomized, open-label, single-dose, two-sequence, two-period crossover study was conducted. Thirty-eight subjects were randomized (1:1) to the TR or RT sequence and received the test (T) and reference (R) formulations in the two study periods separated by an adequate washout. Plasma concentrations of sildenafil and N-desmethyl sildenafil were quantified using high-performance liquid chromatography-tandem mass spectrometry. PK parameters were derived by noncompartmental analysis using Phoenix WinNonlin (version 8.4), and bioequivalence was assessed based on the geometric mean ratios (GMRs; T/R) and their 90% confidence intervals (CIs) for sildenafil C_max, AUC_0–t, and AUC_0–∞. All 38 subjects completed the study. Following administration of T and R, the mean ± SD C_max of sildenafil was 319.08 ± 124.07 and 334.89 ± 189.28 ng/mL, respectively; AUC_0–t was 838.10 ± 351.13 and 823.64 ± 346.63 h ng/mL; and AUC_0–∞ was 872.05 ± 360.26 and 856.12 ± 357.16 h ng/mL. For N-desmethyl sildenafil, the mean ± SD C_max was 171.97 ± 70.05 and 168.67 ± 64.07 ng/mL; AUC_0–t was 708.51 ± 372.91 and 667.19 ± 315.07 h ng/mL; and AUC_0–∞ was 746.10 ± 378.76 and 705.23 ± 329.39 h ng/mL, respectively. The 90% CIs for the GMRs (T/R) of sildenafil C_max, AUC_0–t, and AUC_0–∞ were 92.69%–106.36%, 97.26%–106.81%, and 97.39%–106.76%, respectively, all within the predefined bioequivalence range of 80.00%–125.00%. These results demonstrate that the test and reference formulations are bioequivalent with respect to the rate and extent of absorption in Chinese subjects under fasting conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316555","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}