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.

Comparative Effectiveness of Bimekizumab in Psoriatic Arthritis: A Model-Based Meta-Analysis of American College of Rheumatology Response Criteria
Clin Pharmacol Ther. 2023 Dec 10. doi: 10.1002/cpt.3135. Online ahead of print.ABSTRACTA model-based meta-analysis (MBMA) was conducted to compare the efficacy of bimekizumab with other psoriatic arthritis (PsA) treatment regimens using ≥20%/50%/70% improvements in American College of Rheumatology (ACR) criteria (ACR20/50/70) for patients with PsA. Forty-nine trials of 16 drugs were identified in the literature, comprising 21,340 patients. Trial-level covariates including prior biologic use, concomitant methotrexate use, time since diagnosis, trial completion year, and active comparator were considered for exploratory mo...
Source: Clinical Pharmacology and Therapeutics - December 11, 2023 Category: Drugs & Pharmacology Authors: Alan Maloney Pinky Dua Ghada F Ahmed Source Type: research

Metabolite Bioanalysis in Drug Development: Recommendations from the IQ Consortium Metabolite Bioanalysis Working Group
This report summarizes the considerations for the trigger, timing, and rigor of bioanalysis in the various assessments to address unique challenges due to metabolites, with respect to efficacy and safety, which may arise during drug development from IND enabling studies, and Phase I, Phase II, and Phase III clinical trials to regulatory submission. The recommended approaches ensure that important drug metabolites are identified in a timely manner and properly characterized for efficient drug development.PMID:38073140 | DOI:10.1002/cpt.3144 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - December 11, 2023 Category: Drugs & Pharmacology Authors: Wenkui Li Faye Vazvaei-Smith Gordon Dear Jason Boer Filip Cuyckens Daniela Fraier Yuexia Liang Ding Lu Heidi Mangus Patricia Moliner Mette Lund Pedersen Andrea A Romeo Douglas K Spracklin David S Wagner Serge Winter Xiaohui Sophia Xu Source Type: research

ISABELA studies: plasma exposure and target engagement do not explain the lack of efficacy of ziritaxestat in patients with IPF
Clin Pharmacol Ther. 2023 Dec 10. doi: 10.1002/cpt.3138. Online ahead of print.ABSTRACTAutotaxin (ATX) contributes to the production of lysophosphatidic acid (LPA), which is associated with fibrosis development in idiopathic pulmonary fibrosis (IPF). The ATX inhibitor, ziritaxestat, failed to reduce decline in forced vital capacity (FVC) in patients with IPF in ISABELA 1 and 2 (NCT03711162; NCT03733444), two identically designed Phase 3 studies. In the current analysis, we evaluated pharmacokinetic and pharmacodynamic data from the pooled ISABELA studies to determine whether the lack of efficacy could be attributed to insu...
Source: Clinical Pharmacology and Therapeutics - December 10, 2023 Category: Drugs & Pharmacology Authors: Amit Taneja Garrit Jentsch St éphane Delage Matthew J Randall Bernt van den Blink Yasmina Bauer Florence Namour Source Type: research

Blood group antigen A carriers exhibit an extended progression-free survival with no more immune-related adverse events
Clin Pharmacol Ther. 2023 Dec 8. doi: 10.1002/cpt.3140. Online ahead of print.ABSTRACTExtensive investigations have been conducted regarding the potential correlation between blood type and the immune system, as well as cancer risk in the Southern Chinese population. However, the prognostic value of the blood group and its genetic determinants in the context of immune checkpoint inhibitor (ICI) treatment remains unclear. Therefore, the associations between the ABO blood group and its single nucleotide polymorphisms (SNPs) were examined in relation to ICI treatment outcomes in 370 eligible patients with cancer. This approac...
Source: Clinical Pharmacology and Therapeutics - December 9, 2023 Category: Drugs & Pharmacology Authors: Chen-Lin Xiao Wen-Hui Liu Zhi-Ying Luo Wen-Ru Li Yi-Ke Li Huan Ren Jian-Quan Luo Source Type: research

Challenging the Norm: A Multidisciplinary Perspective on Intravenous to Subcutaneous Bridging Strategies for Biologics
Clin Pharmacol Ther. 2023 Dec 8. doi: 10.1002/cpt.3133. Online ahead of print.ABSTRACTThe transition from intravenous (IV) to subcutaneous (SC) administration of biologics is a critical strategy in drug development aimed at improving patient convenience, compliance, and therapeutic outcomes. Focusing on the increasing role of model-informed drug development (MIDD) in the acceleration of this transition, an in-depth overview of the essential clinical pharmacology and regulatory considerations for successful IV to SC bridging for biologics after the IV formulation has been approved are presented. Considerations encompass mul...
Source: Clinical Pharmacology and Therapeutics - December 9, 2023 Category: Drugs & Pharmacology Authors: Sihem Ait-Oudhia Yow-Ming Wang Anne-Gaelle Dosne Amit Roy Jin Y Jin Jun Shen Leonid Kagan Flora T Musuamba Lucia Zhang Shinichi Kijima Marc R Gastonguay Daniele Ouellet Source Type: research

Drug-induced Acute Pancreatitis: A Real-world Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database
In this study, we provided the current comprehensive landscape of AP culprit-drugs from the pharmacovigilance perspective, which can provide reference information for clinical practice.PMID:38069538 | DOI:10.1002/cpt.3139 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - December 9, 2023 Category: Drugs & Pharmacology Authors: Dongxuan Li Hongli Wang Chunmeng Qin Dan Du Yalan Wang Qian Du Songqing Liu Source Type: research

The European List of Essential Medicines for Medical Education: a modified Delphi study
Clin Pharmacol Ther. 2023 Dec 7. doi: 10.1002/cpt.3132. Online ahead of print.ABSTRACTRational prescribing is essential for the quality of health care. However, many final-year medical students and junior doctors lack prescribing competence to perform this task. The availability of a list of medicines that a junior doctor working in Europe should be able to independently prescribe safely and effectively without supervision could support and harmonize teaching and training in clinical pharmacology and therapeutics (CPT) in Europe. Therefore, our aim was to achieve consensus on such a list of medicines that are widely access...
Source: Clinical Pharmacology and Therapeutics - December 8, 2023 Category: Drugs & Pharmacology Authors: Erik M Donker Pietro Spitaleri Timpone David J Brinkman Milan C Richir Paraskevi Papaioannidou Robert Likic Emilio J Sanz Thierry Christiaens Jo ão N Costa Fabrizio De Ponti Milo Gatti Ylva B öttiger Cornelis Kramers Rahul Pandit Michiel A van Agtmael J Source Type: research

In Memoriam Michelle A. Rudek (1972 - 2023)
Clin Pharmacol Ther. 2023 Dec 7. doi: 10.1002/cpt.3137. Online ahead of print.NO ABSTRACTPMID:38062790 | DOI:10.1002/cpt.3137 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - December 8, 2023 Category: Drugs & Pharmacology Authors: Sharyn D Baker William D Figg Source Type: research

Machine Learning-led Optimization of Combination Therapy: Confronting the Public Health Threat of Extensively Drug Resistant Gram Negative Bacteria
This study utilized human population PK (PopPK) of aztreonam, ceftazidime/avibactam, and polymyxin B along with in vitro pharmacodynamics from the Hollow Fiber Infection Model (HFIM) to derive optimal multi-drug regimens de novo through implementation of a genetic algorithm (GA). The mechanism-based PD model was constructed based on 7-day HFIM experiments across four clinical, extensively drug resistant K. pneumoniae isolates. GA-led optimization was performed using thirteen different fitness functions to compare the effects of different efficacy (60%, 70%, 80% or 90% of simulated subjects achieving bacterial counts of 102...
Source: Clinical Pharmacology and Therapeutics - December 8, 2023 Category: Drugs & Pharmacology Authors: Nicholas M Smith Thomas D Nguyen Thomas P Lodise Liang Chen Jan Naseer Kaur John F Klem Katie Rose Boissonneault Patricia N Holden Dwayne R Roach Brian T Tsuji Source Type: research

Quantitative Systems Toxicology Modeling Informed Safe Dose Selection of Emvododstat in Acute Myeloid Leukemia Patients
Clin Pharmacol Ther. 2023 Dec 8. doi: 10.1002/cpt.3136. Online ahead of print.ABSTRACTClinical investigation of emvododstat for the treatment of solid tumors was halted after two patients who were heavily treated with other anticancer therapies experienced drug-induced liver failure. However preclinical investigations supported that emvododstat at lower doses might be effective in treating acute myeloid leukemia (AML) and against SARS-CoV-2 as a dihydroorotate dehydrogenase inhibitor. Therefore, a quantitative systems toxicology model, DILIsym, was employed to predict liver safety of the proposed dosing of emvododstat in A...
Source: Clinical Pharmacology and Therapeutics - December 8, 2023 Category: Drugs & Pharmacology Authors: Kyunghee Yang Ronald Kong Robert Spiegel John D Baird Kylie O'Keefe Brett A Howell Paul B Watkins Source Type: research