Journal of Clinical Pharmacology最新文献

{"title":"Drug-Drug Interaction Between Rifampicin and Albuvirtide: A Phase 1, Randomized, Open-Label Study.","authors":"Li Zhang, Jun Chen, Xiao-Yan Lin, Yan Lu, Yan Wu, Yi-Jun Wu, Xian-Min Meng","doi":"10.1002/jcph.6191","DOIUrl":"https://doi.org/10.1002/jcph.6191","url":null,"abstract":"<p><p>Albuvirtide (ABT) is a novel long-acting fusion inhibitor for human immunodeficiency virus type 1 (HIV-1), and may be co-administered with rifampicin (RIF) in patients concurrent with tubercle bacillus and HIV-1. This study was conducted to investigate the pharmacokinetic effect of co-administration of the two drugs. In the study, 24 healthy volunteers were randomized to receive ABT alone or with RIF. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry for RIF and competitive enzyme-linked immunosorbent assay for ABT. Co-administration with RIF increased the maximum concentration (C_max) of ABT by 6.93%, and the area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC_0-t) by 21.31%; the geometric mean ratio values (GMRs) for C_max and AUC_0-t of ABT when co-administered with RIF, relative to administered alone, were 106.93% (90% confidence interval [CI] 97.53%-117.23%) and 121.31% (90% CI 108.68%-135.40%), respectively. Co-administration with ABT decreased the steady-state C_max (C_max,ss) of RIF by 10.19%, and the steady-state AUC from time 0 to 24 h (AUC_{0-24 h,ss}) by 19.93%; the GMRs for C_max,ss and AUC_{0-24 h,ss} of RIF when co-administered with ABT, relative to administered alone, were 89.81% (90% CI, 79.97%-104.79%) and 80.07% (90% CI 75.68%-84.72%), respectively. The time to reach Cmax (Tmax) of both ABT and RIF demonstrated no statistically significant difference, whether administered alone or concurrently. The pharmacokinetics profiles of both RIF and ABT changed to some extent when co-administered, while no clinically significant impact on these two drugs was observed, indicating that ABT and RIF can be used together without necessitating dose adjustments.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the Impact of Diet-and-Exercise-Induced Weight Loss on Drug Metabolism and Gastric Emptying in Patients with Obesity.","authors":"Shuhan Liu, Lu Wang, Nicole Miller, Andrea Waltje, Mohamed Abdelnabi, Hao-Jie Zhu, Duxin Sun, Amy E Rothberg, Manjunath P Pai","doi":"10.1002/jcph.6192","DOIUrl":"https://doi.org/10.1002/jcph.6192","url":null,"abstract":"<p><p>Obesity significantly influences drug pharmacokinetics (PK), which challenges optimal dosing. This study examines the effects of diet-and-exercise-induced weight loss on key drug-metabolizing enzymes and gastric emptying in patients with obesity, who frequently require medications for comorbidities. Participants followed a structured weight management program promoting weight loss over 3-6 months and were not concomitantly on potential CYP inducers or inhibitors. Using a drug cocktail of acetaminophen, caffeine, omeprazole, and midazolam, we assessed UGT1A1, CYP1A2, CYP2C19, and CYP3A4 enzyme activities before and after weight loss, respectively, by measuring parent and metabolite concentrations. The time to maximum acetaminophen plasma concentrations reflected the gastric emptying time. PK profiles were compared across two phases: baseline (Phase 1) and post-weight loss (Phase 2). Twenty-four participants enrolled, 21 completed Phase 1 and 12 completed both phases. Statistically significant (N = 12, P < .05) gains in CYP2C19 and CYP3A4 activity were observed after weight loss of 7.6% to 26.2%, with a median [25th, 75th percentile] increase in activity of 90.5 [15.0, 194.3] % and 43.0 [7.5, 68.0] %, respectively. A 2- or 3-h single plasma sample-based ratio of the metabolite to parent concentration strongly correlated with the respective AUC ratio for the drug metabolism phenotype (N = 21). Our findings provide provisional data for evaluation of the effects of non-pharmacologically and non-surgically induced weight loss on gastric emptying and drug metabolism for future physiologically based PK models. Development of mechanistic models to optimize drug dosing in obesity are necessary since weight and body composition shifts are expected with emerging new treatments.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Cannabis Per Se Laws: A Semi-Mechanistic Pharmacometrics Model for Quantitative Characterization of THC and Metabolites in Oral Users.","authors":"Peizhi Li, Guohua An","doi":"10.1002/jcph.6181","DOIUrl":"https://doi.org/10.1002/jcph.6181","url":null,"abstract":"<p><p>Recreational cannabis use has increased notably in the United States in the past decade, with a recent surge in oral consumption. This trend has raised concerns about driving under the influence. Current cannabis-impaired driving laws lack standardization, with some states implementing blood Δ9-tetrahydrocannabinol (THC) per se limits (1, 2, and 5 ng/mL). However, these limits have been criticized for their inaccuracy and unreliability, highlighting the need for legal refinement. Addressing this issue requires understanding the complex pharmacokinetics (PK) and pharmacodynamics (PD) of THC, cannabis's primary psychoactive component, which can be characterized using a population PK model. However, existing PK models mainly focus on inhalation data and do not account for the growing number of oral cannabis users. To bridge this gap, a semi-mechanistic population PK model was developed using data from 10 published studies following intravenous or oral administration of cannabis to characterize THC and its metabolites in oral users. Simulated THC plasma concentrations for doses from 2.5 mg to 100 mg in frequent and occasional users were used to evaluate the effectiveness of existing per se limits. Results showed that the 1 ng/mL limit was least effective due to a high risk of false positives, while the 2 and 5 ng/mL limits remain inconclusive due to limited PD data linking blood THC levels to impairment. These findings suggest that the existing per se laws may not fully address the complexity of cannabis impairment, underscoring the need for further research and refinement of cannabis-impaired driving laws.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding and Streamlining Dose Finding: From Dose Simulation to Dose Estimation.","authors":"Dominic Bräm, Freya Bachmann, Johannes Schropp, Verena Gotta, Britta Steffens, John van den Anker, Marc Pfister, Gilbert Koch","doi":"10.1002/jcph.6188","DOIUrl":"https://doi.org/10.1002/jcph.6188","url":null,"abstract":"<p><p>Understanding drug dosing to fulfill safety and efficacy requirements in a patient population is an essential part of dose finding in clinical practice and drug development. The majority of current dose finding methods are simulation-based, which can be time consuming and resource intensive. Model-based simulations also do not guarantee that the dose, that will optimally fulfill the safety and efficacy endpoints, will be found. In this work, an advanced dose estimation approach based on the OptiDose concept is utilized to understand therapeutic doses in a patient population and to streamline dose finding. To demonstrate the potential of this concept, two illustrative case studies are presented, each representing specific challenges for dose finding, including different safety and efficacy requirements, complex dose-response relationships, and changes of dynamics in special populations. For both applications, the distributions of therapeutic doses in the population were estimated, such that therapeutic population doses can be determined for any proportion of patients to fulfill the safety and efficacy endpoints. In addition, the therapeutic population dose with which 50% and 95% of the population will fulfill the safety and efficacy requirements was estimated. Dose estimation for both drug applications was implemented in Monolix. The presented OptiDose approach has the potential to identify the \"optimal\" dose for any pharmacometric and clinical pharmacology scenario, allowing to guide clinical practice and facilitate dose selection in drug development, particularly in special populations such as pediatric or cancer patients. As such, we suggest moving from current \"dose simulation\" approaches toward a more efficient \"dose estimation\" paradigm.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Assessment of Drug Transporter Inhibition Using Biomarkers: Review of the Literature (2015-2024).","authors":"David Rodrigues, Stephanie Wezalis","doi":"10.1002/jcph.6183","DOIUrl":"https://doi.org/10.1002/jcph.6183","url":null,"abstract":"<p><p>As part of a narrative review of various publications describing the clinical use of urine- and plasma-based drug transporter biomarkers, it was determined that the utilization of coproporphyrin I, a hepatic organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 biomarker, has been reported for 28 different drug-drug interaction (DDI) perpetrator drugs. Similarly, biomarkers for liver organic cation transporter 1 (isobutyryl-l-carnitine, N = 7 inhibitors), renal organic cation transporter 2 and multidrug and toxin extrusion proteins (N¹-methylnicotinamide, N = 13 inhibitors), renal organic anion transporter (OAT) 1 and 3 (pyridoxic acid, N = 7 inhibitors), and breast cancer resistance protein (riboflavin, N = 3 inhibitors) have also been described. Increased use of biomarkers has also been accompanied by modeling efforts to enable DDI predictions and development of multiplexed methods to facilitate their bioanalysis. Overall, there is consensus that exploratory biomarkers such as coproporphyrin I can be integrated into decision trees encompassing in vitro transporter inhibition data, DDI risk assessments, and follow-up Phase 1 studies. Therefore, sponsors can leverage biomarkers to evaluate dose-dependent inhibition of selected transporters, use them jointly with drug probes to deconvolute DDI mechanisms, and integrate in vitro data packages to establish calibrated (biomarker informed) DDI risk assessment cutoffs. Although transporter biomarker science has progressed, reflected by its inclusion in the recently issued International Council for Harmonisation DDI guidance document (M12), some biomarkers still require further validation. There is also a need for biomarkers that can differentiate specific transporters (e.g., OATP1B3 vs OATP1B1 and OAT1 vs OAT3).</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigator-Initiated Clinical Pharmacokinetic Studies in Resource-Limited Settings: Minimal Requirements and Practical Guidance.","authors":"Aniek Uittenboogaard, Susan Mageto, Sherif Kamal Eldin Mohamed, Bertrand Pourroy, Benjamin Mwesige, Agness Chisomo Chitedze, Gertjan Kaspers, Festus Njuguna","doi":"10.1002/jcph.6184","DOIUrl":"https://doi.org/10.1002/jcph.6184","url":null,"abstract":"<p><p>Clinical pharmacology studies are critical for determining the efficacy and safety of drugs. Due to the resource-intensive nature of these studies, most have been conducted in high-income countries, leading to a significant gap in clinical pharmacology data for patients in low- and middle-income countries. This paper provides an overview of the minimal requirements for performing a clinical pharmacology investigator-initiated trial (IIT), including pharmacokinetic sampling. We identify common challenges in resource-limited settings and propose strategies to overcome them. This guideline covers regulatory approval, participant recruitment, drug storage, sample collection and handling, transport, bioanalytical analysis, and data management tailored to the constraints of resource-limited settings. Strategies are proposed to minimize resource demands, including simplified study designs, the use of technologies like whole blood microsampling, and opportunities for collaboration. The goal is to provide practical guidance for those seeking to perform a clinical pharmacology IIT in resource-limited settings to improve safe and effective drug treatment for patients worldwide. Beyond the scope of this guideline is a detailed step-by-step guide on how to perform clinical pharmacology studies.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Renal OAT3 and Hepatic CYP3A Activities in Pregnant Women with Acute Pyelonephritis Using the Endogenous Biomarker Cortisol and 6β-Hydroxycortisol.","authors":"João Paulo Bianchi Ximenez, Jhohann Richard de Lima Benzi, Julia Cristina Colombari, Matheus de Lucca Thomaz, Adriana Rocha, Ana Cláudia Rabelo E Silva, Patrícia Pereira Dos Santos Melli, Geraldo Duarte, Vera Lucia Lanchote","doi":"10.1002/jcph.6186","DOIUrl":"https://doi.org/10.1002/jcph.6186","url":null,"abstract":"<p><p>This study evaluates the impact of acute pyelonephritis in pregnant women on the in vivo activity of renal OAT3 using the endogenous biomarker (EB) 6β-hydroxycortisol (6β-OHF) renal clearance (CL_renal 6β-OHF) and AUC_6β-OHF validated by correlating with the secretion clearance (CL_sec) of the probe drug furosemide. Additionally, 6β-OHF formation clearance (CL_formation 6β-OHF) as well as urinary (Ae_6β-OHF/Ae_F) and plasma (AUC_6βOHF/AUC_F) ratios were also evaluated as EB for hepatic CYP3A activity. Pregnant women in their third trimester of gestation, diagnosed with acute pyelonephritis, were recruited before (pre-treatment, n = 8) and after (post-treatment, n = 8) cefuroxime treatment and resolution of acute pyelonephritis. All participants received a single dose of furosemide 40 mg for evaluation of OAT3 in vivo activity on both occasions followed by collection of urine and serial blood samples for 24 h. The CL_renal 6β-OHF (geometric mean and 95% CI) increased from 1.81 L/h (0.86-3.83) to 11.82 L/h (6.58-21.24), whereas the AUC_6β-OHF decreased from 44.85 ng h/mL (30.96-64.98) to 24.20 ng h/mL (16.05-36.48) pre- and post-treatment. Significant statistical correlations were observed between furosemide CL_sec and CL_renal 6β-OHF (R = 0.88, P = .01) and AUC_6β-OHF (R = -0.66, P > .001). Additionally, the CL_formation 6β-OHF was lower in pre-treatment 26.81 L/h (10.18-70.59) than in post-treatment 96.18 L/h (64.21-144.09), whereas AUC_6βOHF/AUC_F ratios were decreased from 0.014 (0.010-0.019) pre-treatment to 0.009 (0.006-0.013) post-treatment. Regarding Ae_6β-OHF/Ae_F ratios, no differences were observed between pre-treatment and post-treatment. In conclusion, CL_renal 6β-OHF evaluates renal OAT3 activity when CYP3A is inhibited, whereas CL_formation 6β-OHF evaluates hepatic CYP3A when OAT3 is inhibited, such as in pregnant women with acute pyelonephritis.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologically based Pharmacokinetic/Pharmacodynamic Modeling (PBPK/PD) of Famotidine in Pregnancy.","authors":"Xiaomei I Liu, Dionna J Green, John van den Anker, Homa K Ahmadzia, Joaquin Calderon, Gilbert J Burckart, André Dallmann","doi":"10.1002/jcph.6185","DOIUrl":"https://doi.org/10.1002/jcph.6185","url":null,"abstract":"<p><p>Famotidine, a H₂-receptor antagonist, is commonly used to treat heartburn and gastroesophageal reflux disease during pregnancy. However, information on the pharmacokinetics (PK) of famotidine in pregnant patients is limited since pregnant patients are usually excluded from clinical trials. This study aimed to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for famotidine in non-pregnant and pregnant populations, and to combine it with a pharmacodynamic (PD) model to predict the effect of famotidine on intragastric pH. Clinical data for model evaluation were taken from the literature. The PBPK model successfully predicted famotidine PK in non-pregnant and pregnant populations. The ratio of predicted versus observed PK parameters in non-pregnant populations ranged from 0.66 to 1.33 for the area under the concentration-time curve and from 0.50 to 1.27 for peak concentration (C_max). In the pregnant populations, these ratios were 0.94 and 1.17 for early pregnancy, 0.82 and 1.29 for mid-pregnancy, and 0.72 and 1.06 for late pregnancy, respectively. Compared to the non-pregnant population, famotidine exposure was predicted to be decreased by, on average, 24% in mid-pregnancy and 20% in late pregnancy. The PBPK/PD model adequately captured the increase in intragastric pH observed in non-pregnant adults after famotidine intake and suggested a similar effect in mid- and late pregnancy. High inter-individual variability and minor discrepancies between model predictions and clinical observations indicate a need for further clinical data to reliably inform dosing strategies and therapeutic outcomes for famotidine in pregnant populations.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are Exposure Recommendations for QT Evaluation Being Fulfilled?","authors":"Tsubasa Wakabayashi, Mamoru Narukawa","doi":"10.1002/jcph.6180","DOIUrl":"https://doi.org/10.1002/jcph.6180","url":null,"abstract":"<p><p>Pharmaceutical companies have several options to evaluate drug-induced QT prolongation, often referred to as QT pathways, during clinical development. Current regulatory practices recommend achieving high clinical exposure (HCE) for conventional thorough QT (TQT) studies. An alternative to the TQT study, commonly known as the Q&A 5.1 pathway, recommends a two-fold HCE as the exposure margin for concentration-corrected QT (C-QTc) analysis. To assess the impact of these recommendations, we analyzed the exposure margins of 166 new active substances approved in Japan since 2015. Among these, 28.3% of substances in conventional TQT studies (n = 92) did not achieve HCE, and 50.0% of substances in the C-QTc analysis (n = 22) did not achieve two-fold HCE. In the integrated risk assessment, C-QTc analysis, often incorporated into first-in-human studies, is recommended to cover HCE for substances showing no QT prolongation risks in both in vitro and in vivo non-clinical studies, and we analyzed whether the C_max achieved in single-ascending dose (SAD) and multiple-ascending dose (MAD) studies reached HCE. The result showed that 51.1% and 47.7% of substances did not achieve HCE in SAD and MAD studies, respectively. Our findings highlight the need for dose-ascending strategy targeting two-fold therapeutic exposure to ensure HCE. Insufficient exposure may lead to failure to waive the TQT study, and delays in development timelines. To address these challenges, we propose strategies for optimizing early clinical study designs to meet the exposure recommendations and reduce the risk of additional requirements from the regulatory authorities at a later stage.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Street Pharmacology: Toxico-Dermatology of Injection Drug Use.","authors":"David F Lehmann, Aryana Nazem, Jeanna Marraffa, Ramsay Sami Farah","doi":"10.1002/jcph.6176","DOIUrl":"https://doi.org/10.1002/jcph.6176","url":null,"abstract":"<p><p>Street medicine is a point-of-care, mobile approach that services the needs of unhoused individuals who are otherwise unable to access medical care in traditional settings. The prevalence of injection drug use combines with the pipeline of illicit substances, to produce a constellation of severe, potentially life-threatening dermatological disorders unique to this population. This review applies principles of clinical pharmacology to clarify the mechanisms underlying the dermatological toxicity of xylazine, desomorphine, and 3,4-methylenedioxymethamphetamine (MDMA).</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957189","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}