Clinical Pharmacology in Drug Development最新文献_第8页

Pharmacokinetics and Bioequivalence of Vardenafil Hydrochloride in Healthy Chinese Volunteers 盐酸伐地那非在中国健康志愿者中的药代动力学和生物等效性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-06-10 DOI: 10.1002/cpdd.1432

Sheng He, Xinyi Wu, Wanggang Zhang, Keli Wang, Yu Chen, Zhibo Zheng, Ting Zhang, Lili Chen, Qingqing Duan, Dongyuan He, Binbin Wu

{"title":"Pharmacokinetics and Bioequivalence of Vardenafil Hydrochloride in Healthy Chinese Volunteers","authors":"Sheng He, Xinyi Wu, Wanggang Zhang, Keli Wang, Yu Chen, Zhibo Zheng, Ting Zhang, Lili Chen, Qingqing Duan, Dongyuan He, Binbin Wu","doi":"10.1002/cpdd.1432","DOIUrl":"10.1002/cpdd.1432","url":null,"abstract":"Vardenafil hydrochloride tablet is an inhibitor of phosphodiesterase type 5, primarily for the treatment of erectile dysfunction. This postprandial study evaluated the pharmacokinetics and bioequivalence of the test and reference formulations of vardenafil hydrochloride tablets in healthy Chinese volunteers. An open, randomized, single-center, single-dose, 2-period, 2-sequence bioequivalence test was conducted on 66 healthy subjects under fed conditions. Subjects were randomly assigned to a 20-mg test or reference formulation with a 7-day washout period. Venous blood samples (4 mL) were collected from each subject 25 times spanning predose (0 hour) to 24 hours after dosing. The plasma concentration of vardenafil was determined by high-performance liquid chromatography-tandem mass spectrometry. Sixty-two volunteers completed the study. Under fed conditions, the maximum plasma concentration was 29.1 ng/mL, the area under the concentration–time curve (AUC) from time 0 to the time of the last measurable concentration was 85.3 ng•h/mL, and AUC from time 0 to infinity was 87.1 ng•h/mL. The 90% confidence intervals of the geometric mean ratio of AUC time 0 to the time of the last measurable concentration and AUC from time 0 to infinity were within the bioequivalence acceptance range of 0.80-1.25. The test formulation was a bioequivalent alternative to the reference formulation when taken under fed conditions in healthy Chinese subjects.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 8","pages":"884-889"},"PeriodicalIF":1.5,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced Bioavailability and Reduced Variability of Dasatinib and Sorafenib with a Novel Amorphous Solid Dispersion Technology Platform 利用新型无定形固体分散技术平台提高达沙替尼和索拉非尼的生物利用度并降低其变异性。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-29 DOI: 10.1002/cpdd.1416

Hans Lennernäs, Magnus Brisander, Charlotta Liljebris, Gérald Jesson, Per Andersson

{"title":"Enhanced Bioavailability and Reduced Variability of Dasatinib and Sorafenib with a Novel Amorphous Solid Dispersion Technology Platform","authors":"Hans Lennernäs, Magnus Brisander, Charlotta Liljebris, Gérald Jesson, Per Andersson","doi":"10.1002/cpdd.1416","DOIUrl":"10.1002/cpdd.1416","url":null,"abstract":"Despite clinical advances with protein kinase inhibitors (PKIs), oral administration of many PKIs is associated with highly variable plasma exposure and a narrow therapeutic window. We developed a novel hybrid nanoparticle-amorphous solid dispersion (ASD) technology platform consisting of an amorphous PKI embedded in a polymer matrix. The technology was used to manufacture immediate-release formulations of 2 tyrosine kinase inhibitors (TKIs), dasatinib and sorafenib. Our primary objective was to improve the absorption properties and reduce the pharmacokinetic (PK) variability of each TKI. The PKs of XS004 (dasatinib-ASD, 100 mg tablet) and XS005 (sorafenib-ASD, 2 × 50 mg capsules) were compared with their crystalline formulated reference drugs (140 mg of dasatinib-reference and 200 mg of sorafenib-reference). The in vitro biopharmaceutics of dasatinib-ASD and XS005-granulate showed sustained increased solubility in the pH range 1.2-8.0 compared to their crystalline references. In vivo, XS004 was bioequivalent at a 30% lower dose and showed increased absorption and bioavailability, with 2.1-4.8 times lower intra- and intersubject variability compared to the reference. XS005 had an increased absorption and bioavailability of 45% and 2.2-2.8 times lower variability, respectively, but it was not bioequivalent at the investigated dose level. Taken together, the formulation platform is suited to generate improved PKI formulations with consistent bioavailability and a reduced pH-dependent absorption process.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"985-999"},"PeriodicalIF":1.5,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Model-Informed Drug Development Approach to Design a Phase 3 Trial of Teverelix Drug Product in Advanced Prostate Cancer Patients with Increased Cardiovascular Risk 以模型为依据的药物开发方法，设计 Teverelix 药物产品在心血管风险增加的晚期前列腺癌患者中的 3 期试验。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-17 DOI: 10.1002/cpdd.1415

Chenna Keshava Reddy Sannala, Carol MacLean, Finn Larsen, Steve van Os, Pravin Jadhav, Neal Shore, Alicia K. Morgans, Tochukwu Okwuosa, Joga Gobburu

{"title":"A Model-Informed Drug Development Approach to Design a Phase 3 Trial of Teverelix Drug Product in Advanced Prostate Cancer Patients with Increased Cardiovascular Risk","authors":"Chenna Keshava Reddy Sannala, Carol MacLean, Finn Larsen, Steve van Os, Pravin Jadhav, Neal Shore, Alicia K. Morgans, Tochukwu Okwuosa, Joga Gobburu","doi":"10.1002/cpdd.1415","DOIUrl":"10.1002/cpdd.1415","url":null,"abstract":"Teverelix drug product (DP) is a parenteral gonadotropin-releasing hormone (GnRH) antagonist that has been successfully tested in phase 2 trials for hormone-sensitive advanced prostate cancer (APC) and benign prostatic hyperplasia (BPH). In previous APC trials, teverelix DP was administered as intramuscular (IM) and subcutaneous (SC) injections, using a loading dose and (in a single trial) a maintenance dose. Our objective was to derive an optimal dosing regimen for phase 3 clinical development, using a pharmacometrics modeling approach. Data from 9 phase 2 studies (229 patients) was utilized to develop a population pharmacokinetic (PK) model that described the concentration profile accommodating both IM and SC routes of administration. A 2-compartment model with sequential first-order absorption (slow and fast) and lag times best described the PK profiles of teverelix following SC and IM administration. An indirect response model with inhibition of production rate was fit to describe testosterone (T) concentrations based on physiological relevance. The final population PK–pharmacodynamic model was used to conduct simulations of various candidate dosing regimens to select the optimal dosing regimen to achieve clinical castration (T < 0.5 ng/mL by day 28) and to sustain clinical castration for 26 weeks. Model simulation showed that a loading dose of 360 mg SC and 180 mg IM with a maintenance dose of 360 mg SC 6-weekly (Q6W) starting at day 28 can achieve a ≥95% castration rate up to 52 weeks. This dose regimen was selected for phase 3 clinical development, which includes cardiovascular safety assessment in comparison to a GnRH agonist.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 8","pages":"915-929"},"PeriodicalIF":1.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics of Fipaxalparant, a Small-Molecule Selective Negative Allosteric Modulator of Lysophosphatidic Acid Receptor 1, and the Effect of Food in Healthy Volunteers 健康志愿者体内溶血磷脂酸受体 1 的小分子选择性负异构型调节剂 Fipaxalparant 的药代动力学及食物的影响。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-17 DOI: 10.1002/cpdd.1417

Yang Song, Farah N. Ali, Zhan Ye, Jennifer Zarzoso, John Rogowski, Yajing Sun, Yan Xin

{"title":"Pharmacokinetics of Fipaxalparant, a Small-Molecule Selective Negative Allosteric Modulator of Lysophosphatidic Acid Receptor 1, and the Effect of Food in Healthy Volunteers","authors":"Yang Song, Farah N. Ali, Zhan Ye, Jennifer Zarzoso, John Rogowski, Yajing Sun, Yan Xin","doi":"10.1002/cpdd.1417","DOIUrl":"10.1002/cpdd.1417","url":null,"abstract":"Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN-825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open-label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450-mg single dose under fasted conditions or with a high-fat meal. Multiple-dose PKs for twice-daily dosing of either 300 or 450 mg with low- or high-fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose-proportional manner from 150 to 450 mg. At 450 mg, a high-fat meal increased the maximum observed concentration and area under the curve by approximately 1.9- and 2.1-fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 7","pages":"819-827"},"PeriodicalIF":1.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers DPP-4 抑制剂 HSK7653 在中国健康志愿者首次人体研究中的浓度-QTc 模型。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-17 DOI: 10.1002/cpdd.1418

Xiaoxu Wang, Hongzhong Liu, Cheng Cui, Xiaoye Niu, Haiyan Li, Shu Niu, Pangke Yan, Nan Wu, Fangqiong Li, Qinghe Wu, Kai Chen, Bei Hu, Dongyang Liu

{"title":"Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers","authors":"Xiaoxu Wang, Hongzhong Liu, Cheng Cui, Xiaoye Niu, Haiyan Li, Shu Niu, Pangke Yan, Nan Wu, Fangqiong Li, Qinghe Wu, Kai Chen, Bei Hu, Dongyang Liu","doi":"10.1002/cpdd.1418","DOIUrl":"10.1002/cpdd.1418","url":null,"abstract":"Cofrogliptin (HSK7653) is a long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus with a twice-monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12-lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration-QT interval corrected for heart rate (C-QTc) analysis, we used linear mixed-effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (ΔQTcF). The result showed that a placebo-corrected Fridericia corrected QT interval (ΔΔQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (Cmax) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice-monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 7","pages":"716-728"},"PeriodicalIF":1.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of the Clinical Drug-Drug Interaction Potential of Pritelivir on Transporters and CYP450 Enzymes Using a Cocktail Approach 采用鸡尾酒法评估普利特韦对转运体和 CYP450 酶的临床药物相互作用潜力

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-16 DOI: 10.1002/cpdd.1408

Michiel de Vries, Susanne Bonsmann, Jörg Pausch, Melanie Sumner, Alexander Birkmann, Holger Zimmermann, Dirk Kropeit

{"title":"Evaluation of the Clinical Drug-Drug Interaction Potential of Pritelivir on Transporters and CYP450 Enzymes Using a Cocktail Approach","authors":"Michiel de Vries, Susanne Bonsmann, Jörg Pausch, Melanie Sumner, Alexander Birkmann, Holger Zimmermann, Dirk Kropeit","doi":"10.1002/cpdd.1408","DOIUrl":"10.1002/cpdd.1408","url":null,"abstract":"Pritelivir is a novel viral helicase-primase inhibitor active against herpes simplex virus. In vitro drug-drug interaction studies indicated that pritelivir has the potential for clinically relevant interactions on the cytochrome P450 (CYP) enzymes 2C8, 2C9, 3A4, and 2B6, and intestinal uptake transporter organic anion transporting polypeptide (OATP) 2B1 and efflux transporter breast cancer resistance protein (BCRP). This was evaluated in 2 clinical trials. In 1 trial the substrates flurbiprofen (CYP2C9), bupropion (CYP2B6), and midazolam (CYP3A4) were administered simultaneously as part of the Geneva cocktail, while the substrate celiprolol (OAPT2B1) was administered separately. In another trial, the substrates repaglinide (CYP2C8) and rosuvastatin (BCRP) were administered separately. Exposure parameters of the substrates and their metabolites (flurbiprofen and bupropion only) were compared after administration with or without pritelivir under therapeutic concentrations. The results of these trials indicated that pritelivir has no clinically relevant effect on the exposure of substrates for the intestinal uptake transporter OATP2B1 and the CYP enzymes 3A4, 2B6, 2C9, and 2C8, and has a weak inhibitory effect on the intestinal efflux transporter BCRP. In summary, the results suggest that pritelivir has a low drug-drug interaction potential.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 7","pages":"755-769"},"PeriodicalIF":1.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Hepatic and Renal Impairment on the Pharmacokinetics of Dersimelagon (MT-7117), an Oral Melanocortin-1 Receptor Agonist 肝肾功能损害对口服黑色素皮质素-1 受体激动剂 Dersimelagon (MT-7117) 药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-15 DOI: 10.1002/cpdd.1413

Akihito Ogasawara, Ryosuke Ide, Shinsuke Inoue, Renli Teng, Atsuhiro Kawaguchi

{"title":"Effect of Hepatic and Renal Impairment on the Pharmacokinetics of Dersimelagon (MT-7117), an Oral Melanocortin-1 Receptor Agonist","authors":"Akihito Ogasawara, Ryosuke Ide, Shinsuke Inoue, Renli Teng, Atsuhiro Kawaguchi","doi":"10.1002/cpdd.1413","DOIUrl":"10.1002/cpdd.1413","url":null,"abstract":"Dersimelagon is an orally administered selective melanocortin-1 receptor agonist being investigated for treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis. Dersimelagon is extensively metabolized in the liver, and potential recipients may have liver dysfunction. Further, effects of renal impairment on pharmacokinetic properties should be established in drugs intended for chronic use. Two separate studies (ClinicalTrials.gov: NCT04116476; NCT04656795) evaluated the effects of hepatic and renal impairment on dersimelagon pharmacokinetics, safety, and tolerability. Participants with mild (n = 7) or moderate (n = 8) hepatic impairment or normal hepatic function (n = 8) received a single oral 100-mg dersimelagon dose. Participants with mild (n = 8), moderate (n = 8), or severe (n = 8) renal impairment or normal renal function (n = 8) received a single 300-mg dose. Systemic exposure to dersimelagon was comparable with mild hepatic impairment but higher with moderate hepatic impairment (maximum observed plasma concentration, 1.56-fold higher; area under the plasma concentration-time curve from time 0 extrapolated to infinity, 1.70-fold higher) compared with normal hepatic function. Maximum observed plasma concentration and area under the plasma concentration-time curve from time 0 extrapolated to infinity were similar with moderate renal impairment but higher with mild (1.86- and 1.87-fold higher, respectively) and severe (1.17- and 1.45-fold higher, respectively) renal impairment versus normal renal function. Dersimelagon was generally well tolerated.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 7","pages":"729-738"},"PeriodicalIF":1.5,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics and Bioequivalence of Fixed-Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open-Label Study in Healthy Volunteers 辛伐他汀和依折麦布固定剂量复方片剂的药代动力学和生物等效性：一项针对健康志愿者的随机、交叉、开放标签研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-15 DOI: 10.1002/cpdd.1411

Chuei Wuei Leong, Kar Ming Yee, Tracy Ann Rani, Kheng Jinm Lau, Shahnun Ahmad, Atiqah Amran, Farah Wahidah Mohd Hassan, Naveen Kumar

{"title":"Pharmacokinetics and Bioequivalence of Fixed-Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open-Label Study in Healthy Volunteers","authors":"Chuei Wuei Leong, Kar Ming Yee, Tracy Ann Rani, Kheng Jinm Lau, Shahnun Ahmad, Atiqah Amran, Farah Wahidah Mohd Hassan, Naveen Kumar","doi":"10.1002/cpdd.1411","DOIUrl":"10.1002/cpdd.1411","url":null,"abstract":"The current study aimed to evaluate the bioequivalence of a new generic combination of simvastatin and ezetimibe with the reference formulation. An open-label, randomized, 3-period, 3-sequence, crossover study, including 60 healthy volunteers, was implemented. Participants received the test and reference formulation, each containing 20 mg of simvastatin and 10 mg of ezetimibe as a single-dose tablet, separated by a minimum of 2-week washout periods. Blood samples were collected for 20 time points from predose to 72 hours after the dose. The total ezetimibe assay was carried out using a validated liquid chromatography-tandem mass spectrometry, while unconjugated ezetimibe, simvastatin, and simvastatin β-hydroxy acid determination was done via a validated ultra-performance liquid chromatography-tandem mass spectrometry. Each assay was preceded by a liquid-liquid extraction step. The pharmacokinetic parameters were derived using noncompartmental analysis and then compared between the reference and test formulations via a multivariate analysis of variance. No statistical difference was found in under the concentration-time curve from time 0 to the last quantifiable concentration and maximum concentration of unconjugated ezetimibe, total ezetimibe, and simvastatin between the reference and test formulations. The 90% confidence intervals of unconjugated ezetimibe, total ezetimibe, and simvastatin natural log-transformed under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum concentration were in the range of 80%-125% as per the bioequivalence acceptance criteria. Therefore, the test formulation was bioequivalent to the reference formulation.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 8","pages":"938-946"},"PeriodicalIF":1.5,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioequivalence Study of Atenolol Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions 空腹和进食条件下中国健康受试者服用阿替洛尔片的生物等效性研究

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-14 DOI: 10.1002/cpdd.1414

Yongtao Li, Yingying Huang, Xihua Fu, Jiajing Xia, Jianfen Su, Wenzhao Gu, Weixiong Liu, Jianqing Jian, Zuoheng Xu

{"title":"Bioequivalence Study of Atenolol Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions","authors":"Yongtao Li, Yingying Huang, Xihua Fu, Jiajing Xia, Jianfen Su, Wenzhao Gu, Weixiong Liu, Jianqing Jian, Zuoheng Xu","doi":"10.1002/cpdd.1414","DOIUrl":"10.1002/cpdd.1414","url":null,"abstract":"Atenolol, a cardioselective β1-blocker, exhibits efficacy in treating cardiovascular diseases. We conducted a single-center, randomized, open, single-dose, 2-preparation, 2-cycle, 2-sequence, double-crossover trial with a 7-day washout period to investigate the pharmacokinetics, bioequivalence (BE), and safety of test and reference atenolol tablets (25 mg) in healthy Chinese volunteers. Forty-eight healthy participants were randomized into the fasting and fed arms. After administering a single oral dose of the test or reference formulation (25 mg), plasma atenolol concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were obtained from concentration-time profiles. In total, 23 and 24 individuals were included in the fasting and fed arms, respectively. The mean concentration-time profiles for both formulations were similar, and Cmax, AUC0-t, and AUC0-∞ were within the BE range of 80%-125%. Thirteen adverse events (AEs) were observed in 7 participants in the fasting arm; 1 withdrew from the trial early owing to an AE. In the fed arm, 20 AEs were observed in 8 participants, and none withdrew from the trial. All adverse reactions were grade I, with no serious AEs or deaths. Therefore, the 2 tablets are bioequivalent in healthy Chinese individuals under fasting and fed conditions, supporting their further clinical development.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 8","pages":"870-875"},"PeriodicalIF":1.5,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Carbamazepine on the Pharmacokinetics of Erdafitinib in Healthy Participants 卡马西平对健康参与者服用厄达非替尼的药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-05-13 DOI: 10.1002/cpdd.1412

Pharavee Jaiprasart, Peter Hellemans, Juhui James Jiao, Anne-Gaëlle Dosne, Marc De Meulder, Loeckie De Zwart, Laurane Brees, Wei Zhu

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