Journal of Clinical Pharmacology最新文献_第3页

Clinical Pharmacology Characterization of the First-In-Class Oncolytic Viral Therapy T-VEC in Adults and Pediatric Subjects. 一流溶瘤病毒疗法T-VEC在成人和儿童中的临床药理学特征

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-09-05 DOI: 10.1002/jcph.70102

Xinwen Zhang, Bhavya Balu, Po-Wei Chen, Khamir Mehta, Chuang Li, Vijay V Upreti

{"title":"Clinical Pharmacology Characterization of the First-In-Class Oncolytic Viral Therapy T-VEC in Adults and Pediatric Subjects.","authors":"Xinwen Zhang, Bhavya Balu, Po-Wei Chen, Khamir Mehta, Chuang Li, Vijay V Upreti","doi":"10.1002/jcph.70102","DOIUrl":"https://doi.org/10.1002/jcph.70102","url":null,"abstract":"Oncolytic viruses are an emerging class of immunotherapies for cancer treatment. Talimogene laherparepvec (T-VEC) is a first-in-class oncolytic virus approved globally for advanced melanoma. Herein, we describe the quantitative clinical pharmacology aspects of T-VEC that supported the development of this unique therapy. As a live therapy, the exposure characteristics of T-VEC are vastly different from the pharmacokinetics (PK) of traditional small molecules or therapeutic proteins and were characterized as tumor site oncolytic viral kinetics. Relatively flat relationships between T-VEC dose, lesion exposures, and efficacy were identified based on dose-exposure-response (D-E-R) analyses of 60 adult subjects, indicating that optimal drug effect was achieved over the studied dose range (106-108 plaque forming unit [PFU]/mL); hence, efficacy was not sensitive to dose variations within the range. The relatively flat D-E-R relationship for T-VEC was also beneficial for biopharmaceutic aspects unique for live viruses, including bridging small variations in viral infectivity observed from batch to batch during manufacturing. Additionally, the exposures in pediatric subjects (N = 15) were within the range, although generally lower in medians than adults (N = 60). The primary safety concern of T-VEC-related herpetic infection was evaluated using a mechanistic PK-PD model which indicated minimal infection risk over the up to 5 years follow-up duration. Overall, T-VEC demonstrated favorable PK-PD profiles and was well tolerated in adults and pediatric subjects at the approved dosing regimen. Quantitative clinical pharmacology analyses have supported the optimal development of T-VEC and are poised to accelerate the development of these promising therapeutic oncolytic viruses.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001704","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

Correction to "Physiologically Based Pharmacokinetic Modeling of Vancomycin and its Comparison with Population Pharmacokinetic Model in Neonates". 修正“万古霉素基于生理的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”。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-28 DOI: 10.1002/jcph.70098

引用次数: 0

Population Pharmacokinetics of Nifedipine in High-Altitude and Plain Patients With Hypertension. 高原平原高血压患者硝苯地平的人群药代动力学研究。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-26 DOI: 10.1002/jcph.70087

Yu Li, Shouhua Mu, Qin Huang, Jingyan Jin, Yinlian Tong, Rong Wang, Wenbin Li

{"title":"Population Pharmacokinetics of Nifedipine in High-Altitude and Plain Patients With Hypertension.","authors":"Yu Li, Shouhua Mu, Qin Huang, Jingyan Jin, Yinlian Tong, Rong Wang, Wenbin Li","doi":"10.1002/jcph.70087","DOIUrl":"https://doi.org/10.1002/jcph.70087","url":null,"abstract":"The pharmacokinetic characteristics of drugs are altered under high-altitude hypoxia. We aim to describe the population pharmacokinetics of nifedipine to investigate the effects of high-altitude hypoxia on the pharmacokinetics of nifedipine in hypertensive patients. A total of 206 plasma concentrations were collected from 50 patients with hypertension in plateau areas and 53 in plain areas. The PK of nifedipine in hypertensive patients in the plateau and plain area of China was described using nonlinear mixed-effects modeling. The patient's blood pressure was recorded to evaluate the antihypertensive effect of nifedipine. The pharmacokinetics of nifedipine were described by a one-compartment model with zero-order absorption and first-order elimination. The estimated apparent clearance was 18.74 L/h with 31.91% interindividual variability, and the apparent volume of distribution was 103.88 L with 22.44% interindividual variability. Plateau versus plains were identified as a significant covariate affecting nifedipine pharmacokinetics, particularly in inter-individual clearance rates. The interindividual variability of CL was reduced from 36.26% to 31.91%, and the CL of patients in the plateau area was about 1.35 times higher than that in the plain area. This study may contribute to the rational use of nifedipine in the plateau area.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975485","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

Application of Lactation Physiologically Based Pharmacokinetic Modeling to Predict Milk Exposure of Passively Diffused Drugs. 基于哺乳生理学的药代动力学模型在预测乳汁被动扩散药物暴露中的应用。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-25 DOI: 10.1002/jcph.70093

Ruhul Kayesh, Michelle Pressly, Daphne Guinn, Zhoumeng Lin, Stephan Schmidt, Kiara Fairman, Carrie Ceresa, Elimika Pfuma Fletcher

{"title":"Application of Lactation Physiologically Based Pharmacokinetic Modeling to Predict Milk Exposure of Passively Diffused Drugs.","authors":"Ruhul Kayesh, Michelle Pressly, Daphne Guinn, Zhoumeng Lin, Stephan Schmidt, Kiara Fairman, Carrie Ceresa, Elimika Pfuma Fletcher","doi":"10.1002/jcph.70093","DOIUrl":"https://doi.org/10.1002/jcph.70093","url":null,"abstract":"Physiologically based pharmacokinetic (PBPK) models have gained interest as a tool for predicting drug transfer to human milk and assessing the exposure levels in infants. Our group previously developed an integrated lactation PBPK model framework to understand the transfer of drugs into milk and the resulting exposure in infants. As a part of the framework, the current paper focuses on performance of lactation PBPK models to predict maternal plasma and milk concentrations for drugs that are not substrates of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) transporters-atenolol, escitalopram, and alprazolam. PBPK models for healthy adult subjects were developed for atenolol and escitalopram in Simcyp v23 and verified against clinical data. For alprazolam, the Simcyp library model was used. The built-in lactation compartment in Simcyp was utilized for the three drugs. Atenolol and escitalopram adult healthy PBPK models showed agreement of plasma concentration-time profiles with respective clinical data. The lactation PBPK models predicted milk concentration profiles with reasonable agreement for all three drugs as well. The predicted milk concentration-time profile, milk pharmacokinetic parameters and milk-to-plasma (M/P) ratio of atenolol, alprazolam, and escitalopram were within 2-fold of the reported values, suggesting agreement between simulation and clinical data. The current work shows the potential of lactation PBPK models to predict drug exposure in human milk for drugs that are not P-gp or BCRP substrates. The approach will be further evaluated for drugs that are substrates for these active transporters known to be present in mammary tissues.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975496","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 Impact of Hepatic Impairment on the Pharmacokinetics of Sotorasib and its Major Metabolites: Implications for Dose Adjustment. 肝损害对索氏菌及其主要代谢物药代动力学的临床影响：剂量调整的意义。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-20 DOI: 10.1002/jcph.70095

Mason McComb, Panli Cardona, Caitlin Sampson, Jessica Purkis, Christopher A James, Brett Houk

{"title":"Clinical Impact of Hepatic Impairment on the Pharmacokinetics of Sotorasib and its Major Metabolites: Implications for Dose Adjustment.","authors":"Mason McComb, Panli Cardona, Caitlin Sampson, Jessica Purkis, Christopher A James, Brett Houk","doi":"10.1002/jcph.70095","DOIUrl":"10.1002/jcph.70095","url":null,"abstract":"Sotorasib is a small molecule KRASG12C inhibitor approved for the treatment of KRASG12C mutated locally advanced or metastatic non-small cell lung cancer in adult patients. The effect of hepatic impairment on the pharmacokinetics (PK) of sotorasib and major metabolites M10, M18, and M24, safety, and tolerability after a single oral dose of 960 mg was assessed in a phase 1, parallel-arm, multi-center (US), open-label study. Sotorasib AUCinf ratio for subjects with moderate (n = 7) or severe (n = 4) hepatic impairment relative to normal hepatic function (n = 7) was 0.746 (90% CI: 0.431-1.29) and 1.04 (0.545-1.97), respectively. Cmax ratio for moderate and sever hepatic impairment was 0.955 (0.512-1.78) and 1.43 (0.688-2.96), respectively. Mean t1/2 values for sotorasib were similar in subjects with normal hepatic function and subjects with moderate or severe hepatic impairment. Cmax and AUCinf of M10 and M24 increased, while M18 decreased with increasing severity of hepatic impairment. Treatment-emergent adverse events were mild in severity and no serious adverse events were reported. Overall, moderate or severe hepatic impairment did not considerably affect the exposure of sotorasib, M10, M18, and M24. This data supports that adjustments to sotorasib dosing are not indicated for moderate or severe hepatic impairment.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884143","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

Recent Utilization of Pediatric Extrapolation and Modeling and Simulation Approaches in Pediatric Drug Development in Japan. 日本儿童药物开发中儿童外推和建模与仿真方法的最新应用。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-17 DOI: 10.1002/jcph.70091

Akinori Nakashima, Akihide Tsujimoto, Masako Saito, Jun Takeda, Makiko Natori, Satoshi Shoji

{"title":"Recent Utilization of Pediatric Extrapolation and Modeling and Simulation Approaches in Pediatric Drug Development in Japan.","authors":"Akinori Nakashima, Akihide Tsujimoto, Masako Saito, Jun Takeda, Makiko Natori, Satoshi Shoji","doi":"10.1002/jcph.70091","DOIUrl":"https://doi.org/10.1002/jcph.70091","url":null,"abstract":"In Japan, the percentage of approved drugs with pediatric indications increased to 30% in 2010-2015, but no further increase was observed through 2020. The Ministry of Health, Labor, and Welfare in Japan presented draft future directions to promote pediatric drug development, where the modeling and simulation (M&S) approach was introduced as a tool to support efficacy and safety, utilizing existing data when building a flexible data package for pediatric drug approval. M&S is considered a powerful scientific tool in pediatric drug development using the pediatric extrapolation approach. We examined approval application data packages for pediatric drugs approved in Japan from January 2019 to March 2023, where 95 drug products were identified as pediatric drugs for this survey. Drugs with complete, partial, or no extrapolation accounted for 43.2%, 30.5%, and 26.3% of the total drugs, respectively. M&S was widely used as the major rationale in dose selection for pediatric clinical trials and/or the recommended dosing regimen in drug approval applications for the pediatric population (60.0%). Further use of existing data with extrapolation strategies may lead to the development of flexible and efficient data packages for pediatric drug approval. Since safety profiles may be different between pediatric and adult populations due to age-related factors, pediatric developmental safety should be incorporated into M&S in future assessments. The pharmaceutical industry, regulatory authorities, and academia need to discuss development strategies from an early stage and share lessons learned, thereby facilitating further discussions on efficient pediatric drug development and delivering drugs for children without delay in Japan.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876348","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

Correction to "Population Pharmacokinetic Modeling of Acetaminophen and Metabolites in Children After Cardiac Surgery With Cardiopulmonary Bypass". 修正“对乙酰氨基酚和代谢物在心脏手术后儿童体外循环的人群药代动力学模型”。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-14 DOI: 10.1002/jcph.70078

引用次数: 0

Exposure-Response Modeling and Simulation to Identify Optimal Mavacamten Posology When Coadministered with CYP3A4 and CYP2C19 Inhibitors in Patients with Obstructive HCM. 与CYP3A4和CYP2C19抑制剂共同应用于阻塞性HCM患者的暴露-反应建模和模拟以确定最佳的马伐卡坦Posology

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-12 DOI: 10.1002/jcph.70072

Samira Merali, Haden Bunn, Caroline Sychterz, Manting Chiang, Shilpa Puli, Amy J Sehnert, Bindu Murthy, Joga Gobburu

{"title":"Exposure-Response Modeling and Simulation to Identify Optimal Mavacamten Posology When Coadministered with CYP3A4 and CYP2C19 Inhibitors in Patients with Obstructive HCM.","authors":"Samira Merali, Haden Bunn, Caroline Sychterz, Manting Chiang, Shilpa Puli, Amy J Sehnert, Bindu Murthy, Joga Gobburu","doi":"10.1002/jcph.70072","DOIUrl":"https://doi.org/10.1002/jcph.70072","url":null,"abstract":"Mavacamten, a cardiac myosin inhibitor, is primarily metabolized by the cytochrome P450 (CYP) enzymes CYP2C19 and CYP3A4, and coadministration with strong CYP3A4 or CYP2C19 inhibitors was contraindicated in patients with obstructive hypertrophic cardiomyopathy (HCM) in the US Prescribing Information. This study assessed the safety and efficacy of modifying mavacamten posology to accommodate coadministration with strong CYP3A4 and strong/moderate CYP2C19 inhibitors. Simulations of 5000 virtual patients with obstructive HCM with an equal distribution of CYP2C19 metabolizer phenotypes were performed using population pharmacokinetic and exposure-response modeling approaches. A reference posology and variations thereof were simulated to evaluate long-term (chronic) and short-term (1-week) coadministration with CYP3A4 or CYP2C19 inhibitors. Proportions of patients with left ventricular ejection fraction (LVEF) <50% and Valsalva left ventricular outflow tract gradient (VLVOTg) <30 mm Hg were evaluated to assess safety and efficacy, respectively. Compared with the reference posology, a modified posology, which used a 2.5-mg starting dose with coadministration being stopped if LVEF was <50% at any time when receiving 2.5 mg, resulted in a similar peak proportion of CYP2C19 poor metabolizers and CYP2C19 ultrarapid metabolizers with LVEF <50% when initiating mavacamten with a CYP3A4 or CYP2C19 inhibitor, respectively. Achievement of optimal efficacy was delayed in some patients owing to dose reduction. Initiation of CYP3A4 or CYP2C19 inhibitor treatment in patients receiving stable mavacamten therapy was accommodated through mavacamten dose reduction by one level. Interruption of mavacamten during short-term administration of inhibitors transiently increased VLVOTg for the duration of interruption, with no effect on LVEF.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838342","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

Reversal of Fentanyl-Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene Administered by Auto-Injector Versus Intranasal Naloxone. 自动注射器肌注纳美芬与鼻内纳洛酮逆转芬太尼诱导的健康受试者呼吸抑制

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-12 DOI: 10.1002/jcph.70088

Alessandra Cipriano, Ellie He, Manjunath Shet, Glen Apseloff, Stephen C Harris

{"title":"Reversal of Fentanyl-Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene Administered by Auto-Injector Versus Intranasal Naloxone.","authors":"Alessandra Cipriano, Ellie He, Manjunath Shet, Glen Apseloff, Stephen C Harris","doi":"10.1002/jcph.70088","DOIUrl":"https://doi.org/10.1002/jcph.70088","url":null,"abstract":"As illegally made fentanyl and congeners continue to drive overdose deaths in the US, experts have called for stronger and longer-lasting antagonists. A randomized, 4-period, 2-treatment crossover replicate-design study in healthy moderately-experienced opioid users (n = 24) evaluated the reversal of opioid-induced respiratory depression (OIRD) by intramuscular (IM) nalmefene 1.5 mg administered by auto-injector delivering a formulation developed for faster onset, compared to intranasal (IN) naloxone 4 mg. Fentanyl infusions were administered to induce a 50% reduction in minute ventilation (MV). Reversal of OIRD, pharmacokinetics, and safety were investigated under steady-state fentanyl agonism. For the primary endpoint, nalmefene demonstrated superiority at 5 min with an MV increase of 4.59 L/min, more than twice the 1.99 L/min increase for naloxone (p < .0001). Nalmefene superiority was also demonstrated at 10, 15, 20, and 30 min, while non-inferiority was demonstrated at 2.5 and 90 min. The time-course of mean antagonist concentrations correlated with increases in mean MV, peaking at approximately 5-10 min following nalmefene compared to 20-30 min following naloxone. Decreases in transcutaneous CO2 (TCO2) followed a similar time-course with a slight delay. At each threshold of percent reversal (25%-100%), nalmefene consistently showed a faster time to onset than naloxone. Both antagonist treatments were tolerated with no serious adverse events. This study shows that nalmefene 1.5 mg IM administered by auto-injector achieved a faster onset, higher magnitude, and longer duration of reversal of OIRD compared to naloxone 4 mg IN and represents another option for the treatment of opioid overdose.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838345","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

Population Pharmacokinetic and Exposure-Efficacy Analyses of Valbenazine in Patients with Huntington's Disease: Supporting Dose Selection for Chorea Management. 丙苯那嗪在亨廷顿舞蹈病患者中的人群药代动力学和暴露-疗效分析：舞蹈病管理的支持剂量选择。

IF 2.3 4区医学

Journal of Clinical Pharmacology Pub Date : 2025-08-12 DOI: 10.1002/jcph.70092

Hoa Q Nguyen, Ryan L Crass, Sunny Chapel, Han-Yi Steve Kuan, Gordon Loewen, Satjit Brar

{"title":"Population Pharmacokinetic and Exposure-Efficacy Analyses of Valbenazine in Patients with Huntington's Disease: Supporting Dose Selection for Chorea Management.","authors":"Hoa Q Nguyen, Ryan L Crass, Sunny Chapel, Han-Yi Steve Kuan, Gordon Loewen, Satjit Brar","doi":"10.1002/jcph.70092","DOIUrl":"https://doi.org/10.1002/jcph.70092","url":null,"abstract":"Valbenazine improved chorea in individuals with Huntington's disease compared to placebo in a phase 3, placebo-controlled study (KINECT-HD). Population pharmacokinetics (PK) and exposure-response (E-R) analyses focused on understanding the PK characteristics of valbenazine and its active metabolite, [+]-α-dihydrotetrabenazine ([+]-α-HTBZ), and their correlation with clinical efficacy measured by the total maximal chorea (TMC) score. Consistent with previous analyses, a two-compartmental population PK model adequately described valbenazine and [+]-α-HTBZ plasma disposition, generating reliable individual-predicted exposure levels for sequential E-R analysis. The distributions of individual-predicted steady-state exposures of valbenazine and [+]-α-HTBZ were found to largely overlap between patients with tardive dyskinesia and those with Huntington's disease (HD) chorea. The relationship between the change from baseline in TMC score and [+]-α-HTBZ systemic exposure were effectively characterized by a nonlinear Emax model, with negligible impact from selected covariates. The predicted E-R curve closely aligns with the observed data, exhibiting a negative slope that indicates an increasing clinical response with escalating doses of 40, 60, and 80 mg/day. Predicted efficacy appears to reach a plateau at 80 mg once daily (QD), suggesting minimal additional benefit beyond this dosage. Together, results from the population PK model and E-R analyses reinforce the evidence base for valbenazine efficacy in reducing chorea severity, as demonstrated by the notable decrease in TMC scores compared to baseline. They also endorse the selection of dosing regimens ranging from 40 to 80 mg QD for the treatment of chorea in patients with HD.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838344","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