The Journal of Clinical Pharmacology最新文献_第2页

Single-Dose Tolerability and Pharmacokinetics of Onradivir in Chinese Patients with Hepatic Impairment and Healthy Matched Controls 中国肝功能受损患者和健康匹配对照组对奥拉迪韦的单剂量耐受性和药代动力学研究

The Journal of Clinical Pharmacology Pub Date : 2024-09-17 DOI: 10.1002/jcph.6134

Cuiyun Li MD, Haijun Li MD, Jiajia Mai MD, Hong Zhang PhD, Min Wu MD, Yanhua Ding PhD, Jufang Huang PhD

{"title":"Single-Dose Tolerability and Pharmacokinetics of Onradivir in Chinese Patients with Hepatic Impairment and Healthy Matched Controls","authors":"Cuiyun Li MD, Haijun Li MD, Jiajia Mai MD, Hong Zhang PhD, Min Wu MD, Yanhua Ding PhD, Jufang Huang PhD","doi":"10.1002/jcph.6134","DOIUrl":"10.1002/jcph.6134","url":null,"abstract":"This study compared the safety and pharmacokinetics of a single oral dose of onradivir, an inhibitor of polymerase basic protein 2 in influenza A virus, in patients with hepatic impairment and healthy participants with normal hepatic function. Eight participants with mild hepatic impairment (Child-Pugh A), eight participants with moderate hepatic impairment (Child-Pugh B), and eight healthy matched controls were enrolled in this open-label, parallel-group clinical trial. After the administration of 600 mg of onradivir, pharmacokinetic parameters were calculated for each cohort and compared. Onradivir was generally well tolerated by all participants. No serious adverse events (AEs) and no deaths were reported during the study. Six patients with moderate hepatic impairment and three patients with mild hepatic impairment reported AEs, all of which were mild and quickly resolved. Compared with the normal liver function group, the maximum concentration, area under the curve from time zero to the last measurable concentration, and area under the curve from time zero to infinity were 103%, 68.5%, and 69.2% higher, respectively, in the mild hepatic impairment group. In the moderate hepatic impairment group, these increases were 101%, 197%, and 204%, respectively. Overall, there were clinically relevant differences in onradivir exposure between patients with mild or moderate hepatic impairment and normal controls. These data imply that onradivir dose adjustment is warranted in patients with mild or moderate hepatic impairment. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05856513).","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 2","pages":"226-232"},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 Food on the Pharmacokinetics, Safety, and Tolerability of Budesonide Oral Suspension in Healthy Adult Participants: A Randomized Phase 1 Study 食物对布地奈德口服混悬液在健康成人中的药代动力学、安全性和耐受性的影响：随机 1 期研究

The Journal of Clinical Pharmacology Pub Date : 2024-09-12 DOI: 10.1002/jcph.6131

Alexander J. Prokopienko PharmD, PhD, Junyao Wang PhD, Vijay Yajnik MD, Mike Baratta MAHCPM, Nirav K. Desai MD, Camilla A. Richmond MD, Ajit Suri PhD

{"title":"Effect of Food on the Pharmacokinetics, Safety, and Tolerability of Budesonide Oral Suspension in Healthy Adult Participants: A Randomized Phase 1 Study","authors":"Alexander J. Prokopienko PharmD, PhD, Junyao Wang PhD, Vijay Yajnik MD, Mike Baratta MAHCPM, Nirav K. Desai MD, Camilla A. Richmond MD, Ajit Suri PhD","doi":"10.1002/jcph.6131","DOIUrl":"10.1002/jcph.6131","url":null,"abstract":"Budesonide oral suspension (BOS) is a swallowed corticosteroid indicated for 12-week therapy in eosinophilic esophagitis with minimal systemic exposure following administration. We aimed to assess the relative bioavailability of a single dose of BOS administered under fasting and fed (high-fat/high-calorie meal) conditions. Healthy adult volunteers (N = 20) were enrolled in an open-label, single-center, crossover study and were randomized (1:1) to receive a single oral dose of BOS 2.0 mg under fasting or fed conditions, with a 48-h washout period before crossover to the alternative conditions. Serial plasma samples were collected before and up to 24 h after dosing. Pharmacokinetic (PK) parameters were calculated from plasma budesonide concentration–time profiles by noncompartmental analysis. The mean peak budesonide concentration (Cmax) was ∼13% lower under fed than under fasting conditions (604.1 vs 692.9 pg/mL). Areas under the concentration–time curves from dosing to the last measurable budesonide concentration and from dosing to infinity were ∼26% higher and ∼27% higher under fed than fasting conditions (3529 vs 2811 pg h/mL and 3892 vs 3075 pg h/mL, respectively). The median time to peak plasma budesonide concentration was significantly longer (∼1 h) under fed than fasting conditions (2.516 vs 1.286 h, P < .001). Safety and tolerability were also assessed throughout the study; all adverse events were mild or moderate in severity. Despite slight differences in budesonide PK parameters between fed and fasting conditions, the effect of food on systemic exposure to budesonide (BOS formulation) is not expected to be clinically meaningful.","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 2","pages":"217-225"},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcph.6131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 Xeligekimab: An Anti-IL-17A Monoclonal Antibody, in Patients with Moderate to Severe Plaque Psoriasis Xeligekimab：抗IL-17A单克隆抗体在中度至重度斑块状银屑病患者中的应用

The Journal of Clinical Pharmacology Pub Date : 2024-09-10 DOI: 10.1002/jcph.6129

Qingheng Meng BSc, Wei Wang MMSc, Lingxiao Zhang MSc, Haiyang Shi MMSc, Hongxia Liu BSc, Qingshan Zheng PhD, Ling Xu PhD

{"title":"Population Pharmacokinetics of Xeligekimab: An Anti-IL-17A Monoclonal Antibody, in Patients with Moderate to Severe Plaque Psoriasis","authors":"Qingheng Meng BSc, Wei Wang MMSc, Lingxiao Zhang MSc, Haiyang Shi MMSc, Hongxia Liu BSc, Qingshan Zheng PhD, Ling Xu PhD","doi":"10.1002/jcph.6129","DOIUrl":"10.1002/jcph.6129","url":null,"abstract":"Xeligekimab, a recombinant fully human IgG4 monoclonal antibody, has been strategically developed to target IL-17A and is presently in the developmental phase for treating moderate to severe plaque psoriasis. This study aims to investigate the pharmacokinetic profile of Xeligekimab, utilizing data derived from clinical trials specifically conducted in Chinese patients. The study conducted a population pharmacokinetic (PopPK) analysis involving 614 patients with plaque psoriasis. Examined covariates encompassed demographics, baseline laboratory tests, anti-drug antibodies (ADA), injection site, and disease-related baseline characteristics. Model evaluation utilized goodness-of-fit, prediction-corrected visual prediction check, and bootstrap methods. The clinical significance of covariates statistically associated with Xeligekimab was assessed through simulation analysis. The PopPK model of Xeligekimab demonstrated characteristics of a two-compartment model with first-order absorption and linear elimination. Inter-individual variability (IIV) was estimated for clearance and volume of distribution. For a typical plaque psoriasis patient, the estimated values for absorption rate constant (Ka), apparent clearance (CL/F), central compartment volume (Vc/F), peripheral compartment volume (Vp/F), and inter-compartmental clearance (Q/F) was 0.225 per day, 2.223 L/day, 4.02 L, 4.13 L, and 1.11 L/day, respectively. The estimated IIV for CL/F and Vc/F was 25.8% and 49.8%, respectively. The elimination half-life (t1/2) was approximately 28.5 days. CL/F was significantly influenced by factors such as body weight, age, gender, and baseline total protein. Vc/F was significantly influenced by body weight, age, gender, and baseline albumin. However, the clinical relevance of these covariate effects on exposure parameters was determined to be limited.","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 1","pages":"53-65"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Incidence of Acute Kidney Injury in Trough and AUC/MIC Vancomycin Dosing Strategies in a Large Tertiary Care Center: A Retrospective Cohort 一家大型三级医疗中心的万古霉素给药策略在低浓度和 AUC/MIC 万古霉素急性肾损伤中的发生率：回顾性队列

The Journal of Clinical Pharmacology Pub Date : 2024-09-05 DOI: 10.1002/jcph.6130

Rafael Ruiz-Gaviria MD, Sarah J. Norman PharmD, BCPS, Sarah H. Elgendi MBA, BCPS, Jiling Chou MA, Sheena Ramdeen MD, MPH

{"title":"Incidence of Acute Kidney Injury in Trough and AUC/MIC Vancomycin Dosing Strategies in a Large Tertiary Care Center: A Retrospective Cohort","authors":"Rafael Ruiz-Gaviria MD, Sarah J. Norman PharmD, BCPS, Sarah H. Elgendi MBA, BCPS, Jiling Chou MA, Sheena Ramdeen MD, MPH","doi":"10.1002/jcph.6130","DOIUrl":"10.1002/jcph.6130","url":null,"abstract":"Acute kidney injury (AKI) is a complication associated with vancomycin use. There is evidence that this was related to the presence of supratherapeutic vancomycin levels rather than the drug itself. The area under the curve over 24 h to minimum inhibitory concentration (AUC/MIC) dosing for vancomycin has replaced trough-based dosing, but the impact of this change on AKI rates remains unclear. A retrospective cohort study was conducted in a tertiary care teaching hospital. Patients from the trough cohort were recruited from January 1, 2019, to June 30, 2019, and the AUC/MIC cohort from July 1, 2021, to January 1, 2022. Sociodemographics, clinical characteristics, and concomitant medications were obtained. AKI was defined by The Kidney Disease Improving Global Outcomes. A total of 1056 patients were included, 509 in the trough cohort and 547 in the AUC/MIC cohort. The baseline rates of chronic kidney disease were 15.4% and 9.9%, respectively. The AKI rates were 15.9% and 11.9% for trough and AUC/MIC cohorts, respectively (P-value .045). The most frequent nephrotoxins were piperacillin/tazobactam (TZP), diuretics, and IV contrast for both groups. The rates of supratherapeutic levels were higher in the trough cohort (20.7%) than in the AUC/MIC cohort (6.6%). The multivariate logistic regression analysis showed that trough dosing was not associated with increased rates of AKI (OR = 0.96 CI 0.64-1.44). Supratherapeutic levels (OR = 4.64), diuretics (OR = 1.62), TZP (OR = 2.01), and ICU admission (OR = 1.72) were associated with AKI. Vancomycin AUC/MIC dosing strategy was associated with decreased rates of supratherapeutic levels of this drug compared to trough dosing, with a trend toward lower rates of AKI.","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 2","pages":"190-196"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Model-Based Approach Supporting Abacavir/Dolutegravir/Lamivudine Fixed-Dose Combination Approval in Children Living with HIV-1 基于模型的方法支持阿巴卡韦/多曲拉韦/拉米夫定固定剂量复方制剂在儿童 HIV-1 感染者中的应用。

The Journal of Clinical Pharmacology Pub Date : 2024-09-05 DOI: 10.1002/jcph.6128

Hardik Chandasana PhD, Ann M. Buchanan MD, Michael McKenna MBChB, Cindy Brothers MSPH, Stephen Hyatt BS, Kimberly Adkison PhD, Navin Goyal PhD, Lionel K. Tan MBBS, PhD

{"title":"A Model-Based Approach Supporting Abacavir/Dolutegravir/Lamivudine Fixed-Dose Combination Approval in Children Living with HIV-1","authors":"Hardik Chandasana PhD, Ann M. Buchanan MD, Michael McKenna MBChB, Cindy Brothers MSPH, Stephen Hyatt BS, Kimberly Adkison PhD, Navin Goyal PhD, Lionel K. Tan MBBS, PhD","doi":"10.1002/jcph.6128","DOIUrl":"10.1002/jcph.6128","url":null,"abstract":"In March 2022, the US Food and Drug Administration expanded indications of TRIUMEQ, a once-daily fixed-dose combination (FDC) containing abacavir (ABC), dolutegravir (DTG), and lamivudine (3TC) to include pediatric patients weighing at least 10 kg for the treatment of HIV-1. Prior to this extension, the ABC 600 mg/DTG 50 mg/3TC 300 mg FDC tablet was approved for use only in the adult/adolescent population, weighing ≥40 kg while each component of the FDC was approved for its use in pediatric patients at least 3 months and older. A new child-friendly formulation was developed as an FDC dispersible tablet (DT) of ABC 60 mg/DTG 5 mg/3TC 30 mg for pediatric patients with a body weight ≥ 6 kg. The present work demonstrates the utility of applying a model-informed drug development (MIDD) approach to expedite ABC/DTG/3TC FDC approval for pediatric patients (≥10 to <40 kg) based on data from the existing individual components and formulation bridging. Population pharmacokinetic models developed for pediatric participants across all three components of ABC/DTG/3TC FDC were employed for exposure prediction and incorporated relative bioavailability data. The predicted plasma exposures of ABC, DTG, and 3TC for FDC doses were consistent with those observed for the single entities in pediatric and adult studies. Thus, safety and efficacy observed in the individual component studies could be adequately extrapolated to the FDC that results in similar exposure. The current work demonstrates the significance of MIDD approaches in facilitating expedited access to child-friendly formulations in the HIV-1 therapeutic area.","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 1","pages":"18-27"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy of Low-Dose Scopolamine and Palonosetron in Reducing Immediate Post-Gastrointestinal Endoscopy Nausea and Vomiting: A Prospective, Randomized, Controlled Study 小剂量东莨菪碱和帕洛诺司琼减轻消化道内窥镜检查后即刻恶心和呕吐的疗效：一项前瞻性随机对照研究。

The Journal of Clinical Pharmacology Pub Date : 2024-09-03 DOI: 10.1002/jcph.6127

Jianghuai Lin MM, Zhiming Cai MM, Yingzi Lin MM, Huanghui Wu MD, PhD, Yu Gu MM

{"title":"Efficacy of Low-Dose Scopolamine and Palonosetron in Reducing Immediate Post-Gastrointestinal Endoscopy Nausea and Vomiting: A Prospective, Randomized, Controlled Study","authors":"Jianghuai Lin MM, Zhiming Cai MM, Yingzi Lin MM, Huanghui Wu MD, PhD, Yu Gu MM","doi":"10.1002/jcph.6127","DOIUrl":"10.1002/jcph.6127","url":null,"abstract":"This study aimed to assess the incidence of post-discharge nausea and vomiting (PDNV) following sedation with nalbuphine and etomidate and to evaluate the prophylactic effects of scopolamine in reducing PDNV. A two-stage prospective clinical trial was conducted. The first part involved an observational study of 77 subjects to assess the PDNV incidence post-sedation with nalbuphine, etomidate, and propofol. The second part compared the effectiveness of palonosetron 0.075 mg (P group), scopolamine 0.1 mg (S group), and their combination (PS group) in reducing PDNV. The primary endpoint was the incidence of PDNV within 8 h post-sedation. Secondary outcomes included PDNV frequency and severity at 8–24, 0–24, and 24–48 h and side effects of medications. The incidence of PDNV within 8 h post-sedation was 37.66% (29/77). The PS group showed a significantly lower PDNV rate of 2.56% within 8 h, compared to the P group (35.71%, P < .001), S group (19.64%, P < .001), and control group (38.39%, P < .001), respectively. The S group (19.64%) also had a lower rate than the P group (35.71%, P = .007) and the control group (38.39%, P = .002). Subgroup analysis suggested a potential differential effect of palonosetron in reducing vomiting among male patients undergoing gastrointestinal procedures. The combination therapy was also associated with fewer cases of mild or no nausea and vomiting. In summary, the incidence of PDNV following sedation with nalbuphine and etomidate was notably high. The combination of scopolamine and palonosetron was more effective in preventing PDNV, with implications for improved post-sedation care.","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 1","pages":"132-142"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Physiologically Based Pharmacokinetic Modeling of Vancomycin and its Comparison with Population Pharmacokinetic Model in Neonates 万古霉素的生理药代动力学模型及其与新生儿群体药代动力学模型的比较

The Journal of Clinical Pharmacology Pub Date : 2024-09-03 DOI: 10.1002/jcph.6126

Ailing Cao MD, Qiaoxi Li MD, Minzhen Han PhD, Qian Liu PhD, Heng Liang PhD, Lu Tan PhD, Yanping Guan PhD

{"title":"Physiologically Based Pharmacokinetic Modeling of Vancomycin and its Comparison with Population Pharmacokinetic Model in Neonates","authors":"Ailing Cao MD, Qiaoxi Li MD, Minzhen Han PhD, Qian Liu PhD, Heng Liang PhD, Lu Tan PhD, Yanping Guan PhD","doi":"10.1002/jcph.6126","DOIUrl":"10.1002/jcph.6126","url":null,"abstract":"Vancomycin has a narrow therapeutic window and a high inter-individual pharmacokinetic variability, especially in neonates with fast maturational and pathophysiological changes, that needs individualized dosing. Physiologically based pharmacokinetic (PBPK) model and population pharmacokinetic (PopPK) model are both useful tools in model-informed precision dosing, while the former is under research in application of vancomycin in neonates. This study aimed to develop a PBPK model of vancomycin in adult and pediatric population, and compared it with published PopPK model (priori or Bayesian method) in predicting vancomycin concentration in 230 neonatal patients (postmenstrual age, PMA, 25-45 weeks). The developed PBPK model showed a good fit between predictions and observations. PBPK model and PopPK model are complementary in different clinical scenarios of vancomycin application. The physiological-change description of PBPK model showed a superior advantage in initial dosing optimization. As for subsequent dose optimization, PopPK Bayesian forecasting performed better than the PBPK estimation in neonates. However, initial precision dosing tools for early neonates (with PMA < 36 weeks) still need further exploitation.","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 1","pages":"87-95"},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics and Safety of Cilofexor and Firsocostat in Healthy Japanese and Non-Japanese Participants 健康日本人和非日本人服用西洛非索和非索司他的药代动力学和安全性。

The Journal of Clinical Pharmacology Pub Date : 2024-08-30 DOI: 10.1002/jcph.6114

Islam R. Younis PhD, FCP, Cara Nelson PhD, Elijah J. Weber PhD, Gong Shen PhD, Ann R. Qin PhD, Deqing Xiao PhD, Timothy R. Watkins MD, MSc, Ahmed A. Othman PhD, FCP

{"title":"Pharmacokinetics and Safety of Cilofexor and Firsocostat in Healthy Japanese and Non-Japanese Participants","authors":"Islam R. Younis PhD, FCP, Cara Nelson PhD, Elijah J. Weber PhD, Gong Shen PhD, Ann R. Qin PhD, Deqing Xiao PhD, Timothy R. Watkins MD, MSc, Ahmed A. Othman PhD, FCP","doi":"10.1002/jcph.6114","DOIUrl":"10.1002/jcph.6114","url":null,"abstract":"Cilofexor, an oral farnesoid X receptor agonist, and firsocostat, an oral, liver-targeted inhibitor of acetyl-coenzyme A carboxylase, are being investigated in combination with semaglutide for the treatment of metabolic dysfunction-associated steatohepatitis (previously known as nonalcoholic steatohepatitis; NCT04971785). The pharmacokinetics and safety profiles of cilofexor (100 mg) and firsocostat (20 mg) were separately investigated in two phase 1 studies, each of which included healthy Japanese participants (n = 20 in the cilofexor study and n = 21 in the firsocostat study) and non-Japanese participants (n = 20 in the cilofexor study and n = 21 in the firsocostat study). Intensive pharmacokinetic sampling was performed over 96 h following a single-dose administration of the study drug. Safety was monitored throughout the study. In total, 39 participants completed each study. The plasma exposures of cilofexor and firsocostat (area under the concentration–time curve [AUC] calculated from time 0 to infinity [AUCinf]) in Japanese participants were 1.24-fold and 1.98-fold, respectively, of those in non-Japanese participants. Both study drugs were well tolerated with no clear differences in adverse events or laboratory abnormalities between Japanese and non-Japanese participants. The approximate 2-fold exposure difference of firsocostat between Japanese and non-Japanese participants at the 20 mg dose does not warrant dose reduction given the previously established safety and tolerability of once-daily doses of firsocostat up to 200 mg.","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"64 12","pages":"1586-1593"},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Real-World Evidence Application in Translational Medicine: Making Use of Prescription Claims to Inform Drug–Drug Interactions of a New Psoriasis Treatment 转化医学中的现实世界证据应用：利用处方索赔来了解牛皮癣新疗法的药物相互作用。

The Journal of Clinical Pharmacology Pub Date : 2024-08-28 DOI: 10.1002/jcph.6118

Casey Kar-Chan Choong PhD, MS, MPH, Jessica Rehmel MS, Amita Datta-Mannan PhD

{"title":"Real-World Evidence Application in Translational Medicine: Making Use of Prescription Claims to Inform Drug–Drug Interactions of a New Psoriasis Treatment","authors":"Casey Kar-Chan Choong PhD, MS, MPH, Jessica Rehmel MS, Amita Datta-Mannan PhD","doi":"10.1002/jcph.6118","DOIUrl":"10.1002/jcph.6118","url":null,"abstract":"Patients with psoriasis often take multiple medications due to comorbidities, raising concerns about drug–drug interactions (DDIs) during the development of new medicines. DDI risk assessments of a new small molecule showed risks of CYP3A4 autoinduction and being a sensitive CYP3A4 substrate. We conducted a real-world evidence (RWE) claims analysis to assess the frequency of prescription claims for up to 12 months from the date of the initial psoriasis diagnosis for drugs that may interact with CYP3A4 substrates. We used 2013 to 2018 patient data from the US Merative MarketScan Research Database. Among patients diagnosed with psoriasis, less than 1% had a claim for a moderate/strong inducer, but up to 15% had a claim for moderate/strong inhibitor. Most prescriptions for CYP3A4 inhibitors or inducers included antibiotics and anticonvulsants. While CYP3A4 inducers were rarely used, those treated received more than >90 days treatment. Then, these RWE data were used to inform the early translational medicine strategy for the new investigational drug by strategically integrating DDI evaluations into a first-in-human healthy volunteer trial prior to studies in patients with psoriasis. The resulting DDI substudy showed that the investigational small molecule did not induce midazolam clearance but was sensitive to CYP3A inhibition, leading to the decision to exclude concomitant use of strong CYP3A4 inducers or inhibitors from clinical trials.","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 1","pages":"66-73"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to “The Association Between Concurrence of Infection and the Onset of Severe Eruption or Liver Injury in Patients Using Antipyretic Analgesics: A Matched, Nested Case-Control Study” 对 "使用解热镇痛药的患者同时感染与发生严重感染或肝损伤之间的关系：一项匹配、嵌套病例对照研究"。

The Journal of Clinical Pharmacology Pub Date : 2024-08-27 DOI: 10.1002/jcph.2497

引用次数: 0