Clinical Pharmacology and Therapeutics This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

The Impact of Regulatory Reforms in China on Drug Lag: The Role of Clinical Development Strategies
This study explores the reasons for drug lag by assessing the impact of reforms in China's drug review system, particularly focusing on the influence of clinical development strategies. This study selected drugs first launched in the United States between 2017 and 2022, examining absolute and relative lag between China and the first-launch country (including submission and review lag). These delays with drugs approved in the European Union and Japan during the same period were compared with uncover the roots of delays in China, further identifying potential factors that could reduce these delays. The results indicate that ...
Source: Clinical Pharmacology and Therapeutics - March 2, 2024 Category: Drugs & Pharmacology Authors: Yue Han Rong Jiang Jinlian Li Yifei Wang Rong Shao Jinping Xie Source Type: research

Physiologically Based Pharmacokinetic Modeling to Investigate the Disease-Drug-Drug Interactions between Voriconazole and Nirmatrelvir/Ritonavir in COVID-19 Patients with CYP2C19 Phenotypes
In conclusion, COVID-19-induced IL-6 elevation and ritonavir increased voriconazole exposure, and the magnitude of interactions was influenced by CYP2C19 phenotype. Thus, caution is warranted when prescribing voriconazole concomitantly with Paxlovid in patients with COVID-19.PMID:38429919 | DOI:10.1002/cpt.3222 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 2, 2024 Category: Drugs & Pharmacology Authors: Peile Wang Shuaibing Liu Jing Yang Source Type: research

Genetic Determinants of Thiazide-Induced Hyperuricemia, Hyperglycemia, and Urinary Electrolyte Disturbances - A Genome-Wide Evaluation of the UK Biobank
In conclusion, we used a two-stage approach to detect two biologically plausible genetic loci that can interact with thiazides to increase the risk of thiazide-associated biochemical abnormalities. Understanding how environmental exposures (including medications such as thiazides) and genetics interact, is an important step toward precision medicine and improved patient outcomes.PMID:38425181 | DOI:10.1002/cpt.3229 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 1, 2024 Category: Drugs & Pharmacology Authors: Innocent G Asiimwe Lauren Walker Reecha Sofat Andrea L Jorgensen Munir Pirmohamed Multimorbidity Mechanism and Therapeutic Research Collaborative (MMTRC) Source Type: research

All that Glitters Is not Gold: Type-I Error Controlled Variable Selection from Clinical Trial Data
Clin Pharmacol Ther. 2024 Feb 28. doi: 10.1002/cpt.3211. Online ahead of print.ABSTRACTClinical trials are primarily conducted to estimate causal effects, but the data collected can also be invaluable for additional research, such as identifying prognostic measures of disease or biomarkers that predict treatment efficacy. However, these exploratory settings are prone to false discoveries (type-I errors) due to the multiple comparisons they entail. Unfortunately, many methods fail to address this issue, in part because the algorithms used are generally designed to optimize predictions and often only provide the measures use...
Source: Clinical Pharmacology and Therapeutics - February 29, 2024 Category: Drugs & Pharmacology Authors: Manuela R Zimmermann Mark Baillie Matthias Kormaksson David Ohlssen Konstantinos Sechidis Source Type: research

Asia-Inclusive Global Development of Enpatoran: Results of an Ethno-Bridging Study, Intrinsic/Extrinsic Factor Assessments and Disease Trajectory Modeling to Inform Design of a Phase II Multiregional Clinical Trial
Clin Pharmacol Ther. 2024 Feb 28. doi: 10.1002/cpt.3216. Online ahead of print.ABSTRACTEnpatoran is a novel, highly selective, and potent dual toll-like receptor (TLR)7 and TLR8 inhibitor currently under development for the treatment of autoimmune disorders including systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), and myositis. The ongoing phase II study (WILLOW; NCT05162586) is evaluating enpatoran for 24 weeks in patients with active SLE or CLE and is currently recruiting. To support development of WILLOW as an Asia-inclusive multiregional clinical trial (MRCT) according to International Conferen...
Source: Clinical Pharmacology and Therapeutics - February 28, 2024 Category: Drugs & Pharmacology Authors: Lena Klopp-Schulze Sathej Gopalakrishnan Özkan Yalkinoglu Yoshihiro Kuroki Hong Lu Kosalaram Goteti Axel Krebs-Brown Marco Nogueira Filho Ulrike Gradhand Markus Fluck Jamie Shaw Jennifer Dong Karthik Venkatakrishnan Source Type: research

Dosing and Exposure of Vancomycin With Continuous Infusion: A Retrospective Study
This study evaluates whether a dosing regimen of 45 mg/kg/day after a 20 mg/kg loading dose for patients with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min results in adequate exposure. We retrospectively analyzed plasma concentrations from patients treated with vancomycin CI as routine clinical care between February and October 2021. Patients under 18 years old, with renal replacement therapy, reduced creatinine clearance (Chronic Kidney Disease Epidemiology Collaboration < 50 mL min/1.73 m2 ) or outpatient antibiotic therapy were excluded. Dose, renal function, and blood draw procedures were assessed for e...
Source: Clinical Pharmacology and Therapeutics - February 27, 2024 Category: Drugs & Pharmacology Authors: Judith Y M N Derijks-Engwegen Nynke G L Jager Source Type: research

Mechanistic Determinants of Daprodustat Drug-Drug Interactions and Pharmacokinetics in Hepatic Dysfunction and Chronic Kidney Disease: Significance of OATP1B-CYP2C8 Interplay
Clin Pharmacol Ther. 2024 Feb 26. doi: 10.1002/cpt.3215. Online ahead of print.ABSTRACTDaprodustat is the first oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved recently for the treatment of anemia caused by chronic kidney disease (CKD) in adults receiving dialysis. We evaluated the role of organic anion transporting polypeptide (OATP)1B-mediated hepatic uptake transport in the pharmacokinetics (PKs) of daprodustat using in vitro and in vivo studies, and physiologically-based PK (PBPK) modeling of its drug-drug interactions (DDIs) with inhibitor drugs. In vitro, daprodustat showed specific transport by O...
Source: Clinical Pharmacology and Therapeutics - February 26, 2024 Category: Drugs & Pharmacology Authors: Yi-An Bi Samantha Jordan Amanda King-Ahmad Mark A West Manthena V S Varma Source Type: research

A Score to Predict the Clinical Usefulness of Therapeutic Drug Monitoring: Application to Oral Molecular Targeted Therapies in Cancer
This study evaluates a quantitative approach with a score to predict the clinical usefulness of TDM for oMTTs. We identified key parameters for an oMTT's suitability for TDM from standard TDM recommendations. We gathered oMTT pharmacological data, which covered exposure variability (considering pharmacokinetic (PK) impact of food and proton pump inhibitors), technical intricacy (PK linearity and active metabolites), efficacy (exposure-response relationship), and safety (maximum tolerated dose, and exposure-safety relationship). To assess the validity and the relevance of the score and define relevant thresholds, we evaluat...
Source: Clinical Pharmacology and Therapeutics - February 23, 2024 Category: Drugs & Pharmacology Authors: Arthur G éraud David Combarel Christian Funck-Brentano Quentin Beaulieu No ël Zahr Sophie Broutin Jean-Philippe Spano Christophe Massard Benjamin Besse Paul Gougis Source Type: research

Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial
Clin Pharmacol Ther. 2024 Feb 23. doi: 10.1002/cpt.3217. Online ahead of print.ABSTRACTA recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or ...
Source: Clinical Pharmacology and Therapeutics - February 23, 2024 Category: Drugs & Pharmacology Authors: Masahiro Sugawara Sunao Kojima Ichiro Hisatome Kunihiko Matsui Kazuaki Uchiyama Naoto Yokota Eiichi Tokutake Yutaka Wakasa Shinya Hiramitsu Masako Waki Hideaki Jinnouchi Hirokazu Kakuda Takahiro Hayashi Naoki Kawai Hisao Mori Kenichi Tsujita Yusuke Ohya K Source Type: research

Real-World Evidence to Inform Regulatory Decision Making: A Scoping Review
Clin Pharmacol Ther. 2024 Feb 23. doi: 10.1002/cpt.3218. Online ahead of print.ABSTRACTReal-world evidence (RWE) is increasingly considered in regulatory decision making. When, and to which extent, RWE is considered relevant by regulators likely depends on many factors. This review aimed to identify factors that make RWE necessary or desirable to inform regulatory decision making. A scoping review was conducted using literature databases (PubMed, Embase, Emcare, Web of Science, and Cochrane Library) and websites of regulatory agencies, health technology assessment agencies, research institutes, and professional organizatio...
Source: Clinical Pharmacology and Therapeutics - February 23, 2024 Category: Drugs & Pharmacology Authors: Marieke S Jansen Olaf M Dekkers Saskia le Cessie Lotty Hooft Helga Gardarsdottir Anthonius de Boer Rolf H H Groenwold Source Type: research