Clinical Pharmacology in Drug Development最新文献_第10页

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Muscarinic M3 Receptor-Positive Allosteric Modulator ASP8302 Following Single and Multiple Ascending Oral Doses in Healthy Volunteers 在健康志愿者中单次和多次递增口服剂量后，肌卡因 M3 受体阳性异构调节剂 ASP8302 的安全性、耐受性、药代动力学和药效学。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-08-09 DOI: 10.1002/cpdd.1460

Shin Takusagawa, Nicoline Treijtel, Masako Saito, Ingrid Michon, Daisuke Miyatake, Fumio Osaki, Sayuri Guro, Tomasso Fadini, Hisakuni Sekino, Marlous Aarden-Bakker, Kentaro Kuroishi, Jan Willem Olivier van Till, Dorien Groenendaal-van de Meent, Michiel de Vries

{"title":"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Muscarinic M3 Receptor-Positive Allosteric Modulator ASP8302 Following Single and Multiple Ascending Oral Doses in Healthy Volunteers","authors":"Shin Takusagawa, Nicoline Treijtel, Masako Saito, Ingrid Michon, Daisuke Miyatake, Fumio Osaki, Sayuri Guro, Tomasso Fadini, Hisakuni Sekino, Marlous Aarden-Bakker, Kentaro Kuroishi, Jan Willem Olivier van Till, Dorien Groenendaal-van de Meent, Michiel de Vries","doi":"10.1002/cpdd.1460","DOIUrl":"10.1002/cpdd.1460","url":null,"abstract":"ASP8302 is an orally administered positive allosteric modulator of the muscarinic M3 receptor. Two Phase 1 studies were conducted, a first-in-human study in Europe and a Japanese phase 1 study. Both were randomized, participant- and investigator-blinded, placebo-controlled, single and multiple ascending oral doses, parallel group, clinical studies in healthy volunteers. Both studies evaluated safety and pharmacokinetics and also included salivary secretion and pupil diameter as pharmacodynamic assessments. There were no deaths, serious adverse events, or treatment-emergent adverse events reported leading to study discontinuation. There were no clinically relevant findings in any of the laboratory, vital signs, electrocardiogram assessments, or photosensitivity testing following multiple administration of up to 150 mg or up to 140 mg once daily for 14 days in the European first-in-human and Japanese Phase 1 study, respectively. The pharmacokinetics of ASP8302 were approximately linear over the dose range studied. There was no evidence of drug accumulation upon repeated dosing. In both studies, ASP8302 showed a dose-dependent pharmacodynamic effect on saliva production at doses from 100 mg onward, which was maintained during repeated dosing. No effect was observed on pupil diameter. These data supported progression of ASP8302 into Phase 2 clinical trials for further clinical development.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1130-1142"},"PeriodicalIF":1.5,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906127","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

Population Pharmacokinetics of Naloxegol in Pediatric Subjects Receiving Opioids 接受阿片类药物治疗的儿科受试者体内纳洛酮的群体药代动力学。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-08-07 DOI: 10.1002/cpdd.1457

Matthew W. Hruska, Mary Ann Mascelli, Sam Liao, Lori Liao, Patrick Davies, Jennifer Kong, Douglas A. Marsteller

{"title":"Population Pharmacokinetics of Naloxegol in Pediatric Subjects Receiving Opioids","authors":"Matthew W. Hruska, Mary Ann Mascelli, Sam Liao, Lori Liao, Patrick Davies, Jennifer Kong, Douglas A. Marsteller","doi":"10.1002/cpdd.1457","DOIUrl":"10.1002/cpdd.1457","url":null,"abstract":"The pharmacokinetics (PK) of naloxegol were characterized in pediatric subjects, aged 6 months or older to less than 18 years who either have or are at risk of developing opioid-induced constipation following single dose administration. Subjects grouped as aged 12 years or older to less than 18 years, 6 months or older to less than 12 years, and 6 months or older to less than 6 years, received a single oral dose of naloxegol at doses that were estimated to achieve plasma exposures comparable to adult 12.5- or 25-mg doses. Intensive and sparse plasma naloxegol samples were collected to assess naloxegol concentrations. Data were combined with previously collected adult PK data and used to estimate PK parameters using population PK analyses. Naloxegol PK was described using a 2-compartment model with Weibull-type absorption. Neither age nor body weight was identified as a significant covariate indicating similar PK properties in adult and pediatric subjects. PK estimates in the youngest age group were approximately 80% less than those in adults (12.5-mg equivalent dose). Exposures in the other pediatric groups were similar to those in adult equivalent doses. The PK of naloxegol were characterized as linear over the dose range, with no clinically significant covariates and comparable PK characteristics in adults and pediatric subjects aged 6 months or older.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 9","pages":"974-984"},"PeriodicalIF":1.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896965","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

Absorption, Metabolism, and Excretion of [14C]-Labeled Anaprazole: A New Proton Pump Inhibitor, After a Single Oral Administration in Healthy Chinese Male Subjects 一种新型质子泵抑制剂--[14C]标记的阿那普拉唑在中国男性健康受试者中单次口服后的吸收、代谢和排泄：一种新型质子泵抑制剂在中国男性健康受试者口服一次后的吸收、代谢和排泄。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-08-05 DOI: 10.1002/cpdd.1458

Lijun Xie, Yanjun Xu, Wei Liu, Chen Zhou, Lian Guo, Sufeng Zhou, Chen Zhang, Juan Chen, Bei Zhu, Sijia Ding, Huan Li, Lingling Zhang, Li Wang, Lingmei Xu, Feng Shao, Lu Wang

{"title":"Absorption, Metabolism, and Excretion of [14C]-Labeled Anaprazole: A New Proton Pump Inhibitor, After a Single Oral Administration in Healthy Chinese Male Subjects","authors":"Lijun Xie, Yanjun Xu, Wei Liu, Chen Zhou, Lian Guo, Sufeng Zhou, Chen Zhang, Juan Chen, Bei Zhu, Sijia Ding, Huan Li, Lingling Zhang, Li Wang, Lingmei Xu, Feng Shao, Lu Wang","doi":"10.1002/cpdd.1458","DOIUrl":"10.1002/cpdd.1458","url":null,"abstract":"Anaprazole is a proton pump inhibitor. This study aims to elucidate absorption, metabolism, and excretion pathways of anaprazole sodium in the human body. A total of 4 healthy Chinese male subjects were administered a single oral dose of 20 mg/100 µCi of [14C]-anaprazole sodium enteric-coated capsules. The whole blood, plasma, and excreta were analyzed for a total radioactivity (TRA) and metabolite profile. The cumulative radioactivity excretion rate was 93.2%, with 53.3% and 39.9% of the radioactive dose excreted in urine and feces, respectively, and 91.6% of dose recovered within 96 hours after dosing. The parent drug, anaprazole, showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism. Overall, 35 metabolites were identified in plasma, urine, and fecal samples. Anaprazole was the most abundant component in plasma followed by the thioether M8-1, accounting for 28.3% and 16.6%, respectively, of the plasma TRA. Thioether carboxylic acid XZP-3409 (26.3% of urine TRA) and XZP-3409 oxidation and dehydrogenation product M417a (15.1% of fecal TRA) were the major metabolites present in urine and feces, respectively. Anaprazole was undetectable in urine, while fecal samples showed traces (0.07% dose). Blood/plasma ratios of the radioactivity (approximately 0.60) remained consistent over time. Anaprazole showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism, and cytochrome P450 3A4 also contributed to its metabolism in healthy individuals.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1115-1122"},"PeriodicalIF":1.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888713","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

Comparative Bioavailability of a Novel Fixed-dose Combination Etoricoxib and Tramadol 新型固定剂量复方药物依托考昔和曲马多的生物利用度比较

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-31 DOI: 10.1002/cpdd.1456

Lourdes Garza-Ocañas, Christian T. Badillo-Castaneda, Sandra L. Montoya Eguía, María T. Zanatta-Calderón, Julia D. Torres Garza, Marco Vinicio Gómez-Meza, José G. Sander-Padilla, Laura A. Lugo-Sánchez, Kevin F. Rios-Brito, Yulia Romero-Antonio, Jorge González-Canudas

{"title":"Comparative Bioavailability of a Novel Fixed-dose Combination Etoricoxib and Tramadol","authors":"Lourdes Garza-Ocañas, Christian T. Badillo-Castaneda, Sandra L. Montoya Eguía, María T. Zanatta-Calderón, Julia D. Torres Garza, Marco Vinicio Gómez-Meza, José G. Sander-Padilla, Laura A. Lugo-Sánchez, Kevin F. Rios-Brito, Yulia Romero-Antonio, Jorge González-Canudas","doi":"10.1002/cpdd.1456","DOIUrl":"10.1002/cpdd.1456","url":null,"abstract":"Multimodal analgesia is defined as using several drugs or techniques simultaneously to target different pain pathways or receptors to avoid pain propagation. This study evaluated the pharmacokinetic profile and comparative bioavailability of etoricoxib 90 mg and tramadol 50 mg dosing alone (reference drugs) or in a novel fixed-dose combination (test drug) under fasting conditions in Mexican healthy volunteers. This was a randomized, open-label, 3-way, crossover, single-dose, prospective, and longitudinal study with a 14-day washout period. Eligible subjects were healthy Mexican adult volunteers. The drugs were dosing orally, according to the randomization sequence, after 10 hours of fasting and 4 hours before breakfast with 250 mL of water at room temperature. Serial blood samples were collected before and after dosing, both drugs were quantified using high-performance liquid chromatography coupled with tandem mass spectrometry. Forty-two subjects were enrolled and 38 completed the study (28 men and 14 women, mean age 25.2 years, mean weight 66.6 kg). Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed for (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0-t), and (area under the plasma drug concentration-time curve from 0 up to infinity (AUC0-∞) data were within the range of 80%-125%. Non-serious adverse events were observed. The results demonstrate that the pharmacokinetic profile and bioavailability of the etoricoxib/tramadol fixed-dose combination are comparable to those of the reference products.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1253-1259"},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855023","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

Pharmacokinetic and Bioequivalence Evaluation of Dihydroxyaluminum Aminoacetate, Heavy Magnesium Carbonate, and Aspirin Tablets in Healthy Chinese Subjects in the Fasting and Postprandial Conditions 健康中国受试者在空腹和餐后状态下服用二羟基氨基乙酸铝、重质碳酸镁和阿司匹林片剂的药代动力学和生物等效性评价

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-31 DOI: 10.1002/cpdd.1455

Fang Yao, Yingxia He, Pan Lu, Jie Wang, Yafang Xie, Xiuwen Li, Qiangwei Liu, Yang Liu, Dan Cao, Jun Liang, Guan Liu

{"title":"Pharmacokinetic and Bioequivalence Evaluation of Dihydroxyaluminum Aminoacetate, Heavy Magnesium Carbonate, and Aspirin Tablets in Healthy Chinese Subjects in the Fasting and Postprandial Conditions","authors":"Fang Yao, Yingxia He, Pan Lu, Jie Wang, Yafang Xie, Xiuwen Li, Qiangwei Liu, Yang Liu, Dan Cao, Jun Liang, Guan Liu","doi":"10.1002/cpdd.1455","DOIUrl":"10.1002/cpdd.1455","url":null,"abstract":"Dihydroxyaluminum aminoacetate, heavy magnesium carbonate, and aspirin tablets is a new combined aspirin preparation, each containing aspirin (81 mg), dihydroxyaluminum aminoacetate (11 mg), and heavy magnesium carbonate (22 mg). This study was conducted to evaluate the pharmacokinetic (PK) and bioequivalence in healthy Chinese subjects. This randomized, open-label, single-dose, 2-sequence, and 2-period crossover study included 78 healthy volunteers (fasting, n = 36; postprandial, n = 42). Blood samples were collected for PK analysis. Aspirin and salicylic acid concentrations in human plasma were determined by liquid chromatography-tandem mass spectrometry. Safety and tolerability were monitored. There were no significant differences between the test and reference formulations in maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, or AUC from time 0 to infinity. The 90% confidence intervals of the test and reference formulations of maximum plasma concentration, AUC from time 0 to time t, and AUC from time 0 to infinity were within the acceptable range (80%-125%) under fasting and postprandial conditions. All adverse events were mild and no serious adverse events were observed in the study. Both compounds were well tolerated in healthy Chinese volunteers.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1157-1163"},"PeriodicalIF":1.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855024","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

Clinical Implications of Co-administering Apixaban with Key Interacting Medications 阿哌沙班与主要相互作用药物联合用药的临床意义。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-24 DOI: 10.1002/cpdd.1446

Nicholas Favatella, David Dalton, Wonkyung Byon, Samira J. Merali, Christian Klem

引用次数: 0

Effect of Erdafitinib on the Pharmacokinetics of Midazolam and Metformin in Patients With Advanced Solid Tumors Harboring FGFR Gene Alterations 厄达非替尼对携带表皮生长因子受体基因改变的晚期实体瘤患者服用咪达唑仑和二甲双胍药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-24 DOI: 10.1002/cpdd.1445

Wei Zhu, Mahadi Baig, Vahid Naini, Marc De Meulder, Sydney Akapame, Loeckie De Zwart, Nahor Haddish-Berhane, Spyros Triantos

{"title":"Effect of Erdafitinib on the Pharmacokinetics of Midazolam and Metformin in Patients With Advanced Solid Tumors Harboring FGFR Gene Alterations","authors":"Wei Zhu, Mahadi Baig, Vahid Naini, Marc De Meulder, Sydney Akapame, Loeckie De Zwart, Nahor Haddish-Berhane, Spyros Triantos","doi":"10.1002/cpdd.1445","DOIUrl":"10.1002/cpdd.1445","url":null,"abstract":"Erdafitinib, an oral pan-FGFR inhibitor, is used in locally advanced or metastatic urothelial carcinoma for adults with FGFR3 genetic alterations and whose disease progressed following prior systemic therapy. This drug-drug interaction substudy evaluated the effect of erdafitinib on the pharmacokinetics of midazolam (cytochrome P450 3A4 substrate), and metformin (organic cation transporter 2 substrate). Twenty-five patients with advanced solid tumors harboring FGFR gene alterations received pretreatment with single doses of midazolam and metformin, followed by a daily dose of erdafitinib. Drug-drug interaction assessments were performed at erdafitinib steady state following coadministration of single doses of midazolam and metformin, respectively. Geometric mean ratios for maximum plasma concentration and area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity were estimated using linear mixed-effects models (90% confidence interval within 80%-125% indicated no interaction). The 90% confidence intervals of geometric mean ratios for maximum plasma concentration, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity of midazolam (86.3%, 88.5%, and 82.1%), 1-OH midazolam (99.8%, 97.4%, and 101.5%), and metformin (108.7%, 119.0%, and 113.9%) were either contained or slightly outside the 80%-125% interval and not considered clinically meaningful. Adverse events were consistent with the known erdafitinib safety profile; no new safety signals emerged. Thus, repeated dosing of erdafitinib had no clinically meaningful effect on the pharmacokinetics of midazolam or metformin.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 10","pages":"1164-1176"},"PeriodicalIF":1.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751314","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

Pharmacokinetic Profile and Comparative Bioavailability of an Oral Fixed-Dose Combination of Metformin and Acetylsalicylic Acid (Aspirin) 二甲双胍和乙酰水杨酸（阿司匹林）口服固定剂量复方制剂的药代动力学特征和生物利用度比较。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-22 DOI: 10.1002/cpdd.1450

Lourdes Garza-Ocañas, Christian T. Badillo-Castañeda, Sandra L. Montoya-Eguía, Maria T. Zanatta-Calderón, Pedro Lennon Sáenz-Chávez, Julia D. Torres-Garza, Ileana C. Rodriguez-Vazquez, Yulia Romero-Antonio, Kevin F. Rios-Brito, Jorge González-Canudas

{"title":"Pharmacokinetic Profile and Comparative Bioavailability of an Oral Fixed-Dose Combination of Metformin and Acetylsalicylic Acid (Aspirin)","authors":"Lourdes Garza-Ocañas, Christian T. Badillo-Castañeda, Sandra L. Montoya-Eguía, Maria T. Zanatta-Calderón, Pedro Lennon Sáenz-Chávez, Julia D. Torres-Garza, Ileana C. Rodriguez-Vazquez, Yulia Romero-Antonio, Kevin F. Rios-Brito, Jorge González-Canudas","doi":"10.1002/cpdd.1450","DOIUrl":"10.1002/cpdd.1450","url":null,"abstract":"Patients with diabetes face a 2-4-fold greater cardiovascular risk compared to those without diabetes. Both metformin and acetylsalicylic acid (aspirin) treatment have demonstrated a significant reduction in this risk. This single-center, open-label, sequence randomized, 2 × 2 crossover, single-dose clinical trial evaluated the pharmacokinetics profile and comparative bioavailability of a novel oral fixed-dose combination (FDC) of metformin/acetylsalicylic acid (500/100 mg tablet) versus the reference mono-drugs administered concomitantly, metformin 500 mg tablet and acetylsalicylic acid 100 mg tablet, in 22 healthy Mexican adult volunteers under fasting conditions. Blood samples were collected predose and at specified intervals across a 24-hour period following administration and were analyzed for metformin and salicylic acid using high-performance liquid chromatography coupled with tandem mass spectrometry. Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0-t), and (area under the plasma drug concentration-time cruve from 0 up to infinity (AUC0∞) data were within the range of 80%-125%. The results obtained from the present clinical study demonstrate the comparative bioavailability of the FDC when compared with the coadministration of reference mono-drugs. There were no adverse events or adverse reactions reported throughout the study.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1245-1252"},"PeriodicalIF":1.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733719","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

The Bioequivalence of Abexinostat (CRA-024781) Tosylate Tablets (20 mg) in Chinese Healthy Subjects Under Fasting Conditions 中国健康受试者在空腹条件下服用阿贝司他（CRA-024781）对甲苯磺酰苯胺片（20 毫克）的生物等效性研究。

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-18 DOI: 10.1002/cpdd.1448

Xiang Li, Wenqiang Guo, Jian Chen, Gewen Tan

引用次数: 0

Impact of a High-Fat Meal on the Pharmacokinetics of Sotorasib, a KRAS G12C Inhibitor 高脂餐对 KRAS G12C 抑制剂 Sotorasib 药代动力学的影响

IF 1.5 4区医学

Clinical Pharmacology in Drug Development Pub Date : 2024-07-17 DOI: 10.1002/cpdd.1452

Panli Cardona, Sandeep Dutta, Brett Houk

{"title":"Impact of a High-Fat Meal on the Pharmacokinetics of Sotorasib, a KRAS G12C Inhibitor","authors":"Panli Cardona, Sandeep Dutta, Brett Houk","doi":"10.1002/cpdd.1452","DOIUrl":"10.1002/cpdd.1452","url":null,"abstract":"Sotorasib is a small molecule drug that specifically and irreversibly inhibits the KRAS p.G12C mutant protein. This analysis investigated the impact of a high-calorie high-fat meal on the pharmacokinetics, safety, and tolerability of sotorasib in both healthy volunteers and patients with KRAS G12C advanced solid tumors. Each subject received a single oral dose of 360 or 960 mg of sotorasib under fasted conditions or with a high-fat meal (fed conditions). The geometric least squares means (GLSM) ratios (fed/fasted) for 360 mg of sotorasib Cmax and AUCinf were 1.03 and 1.38, respectively, in healthy volunteers (N = 14). The GLSM ratios (fed/fasted) for Cmax and AUC0-24h were 1.38 and 1.75, respectively, with 360 mg of sotorasib in cancer patients (N = 2). The GLSM ratios (fed/fasted) for Cmax and AUC0-24h were 0.660 and 1.25, respectively, with 960 mg of sotorasib in cancer patients (N = 8). Sotorasib was well tolerated in fast and fed conditions. The impact of a high-fat meal on sotorasib exposure is less than a 2-fold increase or decrease in Cmax and AUCs.","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":"13 11","pages":"1219-1226"},"PeriodicalIF":1.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626231","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