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Better Rejection-Free Survival at Three Years in Kidney Transplant Recipients With Model-Informed Precision Dosing of Mycophenolate Mofetil
Clin Pharmacol Ther. 2024 Feb 19. doi: 10.1002/cpt.3206. Online ahead of print.ABSTRACTThe clinical impact of individual dose adjustment of mycophenolate mofetil is still debated, due to conflicting results from randomized clinical trials. This retrospective study aimed to compare 3-year rejection-free survival and adverse effects between adult kidney transplant recipients (KTRs) with or without mycophenolate mofetil model-informed precision dosing (MIPD). MIPD is defined here as mycophenolic acid area under the curve (AUC0-12h ) estimation using a limited sampling strategy, pharmacokinetic models and Bayesian estimators; ...
Source: Clinical Pharmacology and Therapeutics - February 19, 2024 Category: Drugs & Pharmacology Authors: Claire Villeneuve Antoine Humeau Caroline Monchaud Marc Labriffe Jean-Phillipe Rerolle Lionel Couzi Pierre-Fran çois Westeel Isabelle Etienne Nassim Kamar Mathias B üchler Antoine Thierry Pierre Marquet Source Type: research

Development and Validation of the Pharmacological Statin-Associated Muscle Symptoms Risk Stratification Score Using Electronic Health Record Data
Clin Pharmacol Ther. 2024 Feb 19. doi: 10.1002/cpt.3208. Online ahead of print.ABSTRACTStatin-associated muscle symptoms (SAMS) can lead to statin nonadherence. This paper aims to develop a pharmacological SAMS risk stratification (PSAMS-RS) score using a previously developed PSAMS phenotyping algorithm that distinguishes objective vs. nocebo SAMS using electronic health record (EHR) data. Using our PSAMS phenotyping algorithm, SAMS cases and controls were identified from Minnesota Fairview EHR, with the statin user cohort divided into derivation (January 1, 2010, to December 31, 2018) and validation (January 1, 2019, to D...
Source: Clinical Pharmacology and Therapeutics - February 19, 2024 Category: Drugs & Pharmacology Authors: Boguang Sun Pui Ying Yew Chih-Lin Chi Meijia Song Matt Loth Yue Liang Rui Zhang Robert J Straka Source Type: research

A Generative and Causal Pharmacokinetic Model for Factor VIII in Hemophilia A: A Machine Learning Framework for Continuous Model Refinement
In conclusion, the proposed approach introduces interesting new possibilities for model development. In the context of rare disease, the introduction of generative models facilitates sharing of synthetic data, enabling the iterative improvement of population PK models.PMID:38372445 | DOI:10.1002/cpt.3203 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - February 19, 2024 Category: Drugs & Pharmacology Authors: Alexander Janssen Louk Smalbil Frank C Bennis Marjon H Cnossen Ron A A Math ôt OPTI-CLOT study group and SYMPHONY consortium Source Type: research

Pharmacokinetics, Pharmacodynamics, and Safety of Edoxaban in Pediatric Subjects: A Phase I Single-Dose Study
Clin Pharmacol Ther. 2024 Feb 18. doi: 10.1002/cpt.3196. Online ahead of print.ABSTRACTThis was an open-label, single-dose, phase I study to characterize the pharmacokinetics (PKs), pharmacodynamics (PDs), and safety of edoxaban in pediatric subjects from birth to 18 years at risk for venous thromboembolism (VTE). Children requiring anticoagulant therapy were enrolled into 5 age cohorts (0 to < 6 months (N = 12), 0.5 to < 2 years (N = 13), 2 to < 6 years (N = 13), 6 to < 12 years (N = 13), and 12 to < 18 years (N = 15)) receiving tablet or oral suspension of edoxaban at doses expected to be equivalent to 30 ...
Source: Clinical Pharmacology and Therapeutics - February 18, 2024 Category: Drugs & Pharmacology Authors: Peng Zou Hamim Zahir Anil Duggal Grishma Pandya James Jin Tarek A Leil Source Type: research

Scientific Review of the Proarrhythmic Risks of Oligonucleotide Therapeutics: Are Dedicated ICH S7B/E14 Studies Needed for Low-Risk Modalities?
Clin Pharmacol Ther. 2024 Feb 16. doi: 10.1002/cpt.3204. Online ahead of print.ABSTRACTOligonucleotide therapeutics (ONTs) represent a new modality with unique pharmacological and chemical properties that modulate gene expression with a high degree of target specificity mediated by complementary Watson-Crick base pair hybridization. To date, the proarrhythmic assessment of ONTs has been influenced by International Conference on Harmonization (ICH) E14 and S7B guidance. To document current hERG/QTc evaluation practices, we reviewed US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Approval Packag...
Source: Clinical Pharmacology and Therapeutics - February 16, 2024 Category: Drugs & Pharmacology Authors: Yusheng Qu Kim A Henderson Tod A Harper Hugo M Vargas Source Type: research

Subcutaneous Biologics: Clinical Pharmacology and Drug Development
Clin Pharmacol Ther. 2024 Mar;115(3):385-390. doi: 10.1002/cpt.3179.NO ABSTRACTPMID:38363287 | DOI:10.1002/cpt.3179 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - February 16, 2024 Category: Drugs & Pharmacology Authors: Sihem Ait-Oudhia Joseph Chen Junyi Li Piet H van der Graaf Source Type: research

American Society for Clinical Pharmacology and Therapeutics
Clin Pharmacol Ther. 2024 Mar;115 Suppl 1:S5-S125. doi: 10.1002/cpt.3167.NO ABSTRACTPMID:38353583 | DOI:10.1002/cpt.3167 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - February 14, 2024 Category: Drugs & Pharmacology Source Type: research

Using Machine Learning to Determine a Suitable Patient Population for Anakinra for the Treatment of COVID-19 Under the Emergency Use Authorization
Clin Pharmacol Ther. 2024 Feb 13. doi: 10.1002/cpt.3191. Online ahead of print.ABSTRACTA randomized, double-blind, placebo-controlled study (SAVEMORE trial) provided data to support an Emergency Use Authorization (EUA) of anakinra in hospitalized adults with positive results of direct severe acute respiratory syndrome-coronavirus 2 viral testing with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR). Currently, the suPAR assay is not commercially availa...
Source: Clinical Pharmacology and Therapeutics - February 13, 2024 Category: Drugs & Pharmacology Authors: Qi Liu Raj Nair Ruihao Huang Hao Zhu Austin Anderson Ozlem Belen Van Tran Rebecca Chiu Karen Higgins Jianmeng Chen Lei He Suresh Doddapaneni Shiew-Mei Huang Nikolay P Nikolov Issam Zineh Source Type: research

Model-Based Prediction of Irinotecan-Induced Grade 4 Neutropenia in Cancer Patients: Influence of Incorporating Germline Genetic Factors in the Model
The objective of this study was to assess whether inclusion of germline genetic variants into a population pharmacokinetic/pharmacodynamic model can improve prediction of irinotecan-induced grade 4 neutropenia and identify novel variants of clinical value. A semimechanistic population pharmacokinetic/pharmacodynamic model was used to predict neutrophil response over time in 197 patients receiving irinotecan. Covariate analysis was performed for demographic/clinical factors and 4,781 genetic variants in 84 drug response- and toxicity-related genes to identify covariates associated with neutrophil response. We evaluated the ...
Source: Clinical Pharmacology and Therapeutics - February 12, 2024 Category: Drugs & Pharmacology Authors: Spinel Karas Ron H J Mathijssen Ron H N van Schaik Alan Forrest Tim Wiltshire Robert R Bies Federico Innocenti Source Type: research

A Natural Language Processing Approach towards Harmonized Communication of Uncertainties Identified during the European Medicine Authorization Process
In this study, we therefore present a natural language processing approach to cluster sentences extracted from the sections on uncertainties in EPARs of centrally authorized medicines, as a steppingstone to harmonization of text describing uncertainties. We used a BERT language model together with dimensionality reduction (Uniform Manifold Approximation and Projection (UMAP)) and clustering (Density-Based Spatial Clustering of Applications with Noise (DBSCAN)) to identify semantic similarities between sentences. Clusters were labeled according to an overarching topic by reviewing the semantically similar sentences. Each cl...
Source: Clinical Pharmacology and Therapeutics - February 12, 2024 Category: Drugs & Pharmacology Authors: Stefan Verweij Vincent Haverhoek Erik Bergman Gabriel Westman Lourens T Bloem Source Type: research