Clinical Pharmacology in Drug Development最新文献

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099864","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099863","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148087256","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 2 Deutetrabenazine Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions","authors":"Dayong Xu,&nbsp;Pengkai Wang,&nbsp;Yuan Li,&nbsp;Ping Zhang,&nbsp;Liying Wei,&nbsp;Xiaolian Xiong,&nbsp;Xin Li","doi":"10.1002/cpdd.70054","DOIUrl":"10.1002/cpdd.70054","url":null,"abstract":"<p>Deutetrabenazine, a deuterated vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved for the treatment of Huntington's disease (HD)-related chorea and tardive dyskinesia (TD). However, pharmacokinetics (PK) and bioequivalence (BE) evidence in the Chinese population has been lacking. This single-center, randomized, open-label, single-dose, two-formulation, four-period, fully replicated crossover study evaluated the PK, BE, and safety of test and reference deutetrabenazine 12 mg tablets under fasting and fed conditions in healthy Chinese volunteers. A total of 90 subjects were enrolled (40 fasting; 50 fed), and 88 completed the study. Plasma concentrations of deutetrabenazine and its active metabolites d6-α-dihydrotetrabenazine (d6-α-HTBZ) and d6-β-dihydrotetrabenazine (d6-β-HTBZ) were quantified using a validated liquid chromatography-tandem mass spectrometry method. BE was assessed using average bioequivalence (ABE) or reference-scaled average bioequivalence (RSABE) according to within-subject variability. Under fasting conditions, RSABE was applied for maximum plasma concentration (C_max) and met equivalence criteria (point estimate within 80%–125%, upper confidence interval bound ≤ 0); under fed conditions, as well as for all remaining PK parameters, ABE criteria were met with the 90% confidence interval within the 80%–125% range. Both formulations were well tolerated, with only mild and transient adverse events and no serious safety findings. These results demonstrate that the test and reference deutetrabenazine tablets are bioequivalent in healthy Chinese adults under both nutritional states.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497529","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148087254","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":"Effect of High-Fat Diet on Pharmacokinetics and Incidence of Adverse Reactions of Tacrolimus in Healthy Chinese Participants","authors":"Xiufang Zhu,&nbsp;Lingxue Shi,&nbsp;Lan Yang,&nbsp;Nana Zhang,&nbsp;Yujie Wu,&nbsp;Peihua Yin,&nbsp;Jianxin Wang,&nbsp;Chunhua Zhou","doi":"10.1002/cpdd.70049","DOIUrl":"10.1002/cpdd.70049","url":null,"abstract":"<p>The effects of food on the pharmacokinetics (PKs) and safety of 1 mg Tacrolimus sustained-release Tacrolimus capsules in healthy Chinese subjects were investigated from one bioequivalence trial. The bioequivalence trial was designed as single-center, openlabel, randomized, single-dose, two-sequence, four-period crossover under both fasted and fed conditions. A total of 80 healthy subjects were enrolled. These subjects received a single oral 1 mg dose of Tacrolimus with a 14-day washout between four periods. Serial PK samples were collected and blood concentrations were analyzed using validated high-performance liquid chromatography–mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods. The BE module of WinNonLin was used for statistical analysis of the maximum concentration (C_max), the area under the concentration–time curve from zero to the final measurable concentration (AUC_0–t), and the area under the concentration–time curve from time zero to infinity (AUC_0–∞) of Tacrolimus in blood.</p><p>The mean values of all pharmacokinetic parameters were similar for the T and R formulations under fasting and fed conditions, and the 90% confidence intervals were inside the 80.00%–125.00% range. For both the T and R formulations, the AUC_0–t and AUC_0–∞ values were higher in the fed test than in the fasting one. The incidence of adverse events (AEs) was similar between the fasted and fed states, and no serious AEs were observed. Fasting significantly increased the exposure of Chinese subjects to 1 mg Tacrolimus.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497549","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148087255","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":"Thorough QT Study on the Effect of Therapeutic and Supratherapeutic Dosing of Givinostat in Healthy Volunteers","authors":"Eugenio Mercuri,&nbsp;Barry Byrne,&nbsp;Tracey Willis,&nbsp;John Bourke,&nbsp;Paolo Bettica,&nbsp;Sara Cazzaniga,&nbsp;Hongqi Xue,&nbsp;Borje Darpo","doi":"10.1002/cpdd.70047","DOIUrl":"10.1002/cpdd.70047","url":null,"abstract":"<p>Givinostat is a class I/II histone deacetylase inhibitor indicated for Duchenne muscular dystrophy (DMD). The study evaluated the effect of therapeutic and supratherapeutic givinostat doses on the QT/QTc interval. Healthy volunteers received each treatment—givinostat hydrochloride monohydrate oral suspension as a therapeutic (100 mg) or supratherapeutic (300 mg) dose, placebo oral suspension, or moxifloxacin oral tablet (positive control, 400 mg)—according to a block randomization scheme. Cardiodynamic assessments were paired with pharmacokinetic samples. A small, clinically non-relevant effect on mean placebo-corrected, change-from-baseline QTcF (∆∆QTcF) of 5.5 ms was seen after givinostat 100-mg dose. Clinically relevant QTc prolongation was observed with the supratherapeutic dose, with a mild ∆∆QTcF increase of 13.6 ms. A delay of ≈3 h between T_max and the largest effect on the QTc interval was seen for both doses. In the concentration-QTc analysis, an E_max model captured the data better than the prespecified linear model and showed that an effect on ∆∆QTcF exceeding 10 ms could be excluded within the full range of observed givinostat concentrations in this study and up to ≈745 ng/mL. Givinostat at the maximum labeled dose (up to 53.2 mg twice daily for DMD) is not expected to pose a QT prolongation risk.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497463","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 Evaluation of a Fixed-Dose Combination of Pelubiprofen and Tramadol: A Randomized Crossover Relative Bioavailability Trial and a Fixed-Sequence Food-Effect Study in Healthy Volunteers","authors":"Bui Thi Tham,&nbsp;Tran Thi Ngan,&nbsp;Tran Van Anh,&nbsp;Kim Dong Chool,&nbsp;Lee Ah Ram,&nbsp;Park Sang Wook,&nbsp;Lee Soo Bok,&nbsp;Oh Dong Ho,&nbsp;Nguyen Van Khai,&nbsp;Nguyen Thi Thu Phuong","doi":"10.1002/cpdd.70050","DOIUrl":"10.1002/cpdd.70050","url":null,"abstract":"<p>DW-1021 is a novel fixed-dose combination salt formulation containing pelubiprofen 45 mg and tramadol hydrochloride 45.9 mg (equivalent to 40.3 mg tramadol free base). Two open-label, phase I clinical studies were conducted in healthy Vietnamese male volunteers to characterize the pharmacokinetics of DW-1021. The relative bioavailability study employed a randomized, single-dose, two-period, two-sequence crossover design (n = 14) comparing DW-1021 with co-administration of Pelubi CR (pelubiprofen 45 mg) and Zytram CR (tramadol hydrochloride 75 mg, equivalent to 65.9 mg tramadol base) under fasting conditions. The food effect study used a fixed-sequence, two-period design (n = 14) to evaluate DW-1021 under fasting and fed (high-fat, high-calorie) conditions. In the relative bioavailability study, DW-1021 resulted in lower exposure to pelubiprofen (AUC_0-t GMR: 86.68%) and generally comparable exposure to trans-OH-pelubiprofen (AUC_0-t GMR: 108.74%) compared with the reference treatment. For tramadol, unadjusted comparisons showed a higher peak concentration (C_max GMR: 192.17%) but lower overall exposure (AUC_0-t GMR: 79.30%). After dose normalization, tramadol exposure per unit dose was higher (AUC_0-t/Dose GMR: 129.58%). In the food effect study, fasting conditions were associated with higher C_max and AUC_0-t of pelubiprofen (GMRs: 109.92% and 140.48%, respectively). Food increased tramadol C_max, while AUC_0-t remained largely comparable between conditions. All adverse events were mild to moderate, and no serious adverse events were reported. In conclusion, DW-1021 exhibited analyte-dependent pharmacokinetic differences relative to the reference treatment. Food intake primarily reduced pelubiprofen exposure, while tramadol AUC_0-t was minimally affected, with a modest increase in C_max under fed conditions.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442837","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"15 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148075321","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}