CPT: Pharmacometrics and Systems Pharmacology 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.

A Markov model of fibrosis development in nonalcoholic fatty liver disease predicts fibrosis progression in clinical cohorts
AbstractDisease progression in nonalcoholic steatohepatitis (NASH) is highly heterogenous and remains poorly understood. Fibrosis stage is currently the best predictor for development of end-stage liver disease and mortality. Better understanding and quantifying the impact of factors affecting NASH and fibrosis is essential to inform a clinical study design. We developed a population Markov model to describe the transition probability between fibrosis stages and mortality using a unique clinical nonalcoholic fatty liver disease cohort with serial biopsies over 3 decades. We evaluated covariate effects on all model paramete...
Source: CPT: Pharmacometrics and Systems Pharmacology - October 3, 2023 Category: Drugs & Pharmacology Authors: Jane Kn öchel, Linnéa Bergenholm, Eman Ibrahim, Stergios Kechagias, Sara Hansson, Mathias Liljeblad, Patrik Nasr, Björn Carlsson, Mattias Ekstedt, Sebastian Ueckert Tags: ARTICLE Source Type: research

Quantitative systems pharmacology in the age of artificial intelligence
(Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - October 2, 2023 Category: Drugs & Pharmacology Authors: Benjamin Ribba Tags: PERSPECTIVE Source Type: research

Population Pharmacokinetic ‐Pharmacodynamic Modeling of Clopidogrel for Dose Regimen Optimization based on CYP2C19 Phenotypes: A Proof of Concept Study
AbstractClopidogrel is an antiplatelet drug used to reduce the risk of acute coronary syndrome and stroke. It is converted by CYP2C19 to its active metabolite; therefore, poor metabolizers (PM) of CYP2C19 exhibit diminished antiplatelet effects. Herein, we conducted a proof of concept study for using population pharmacokinetic-pharmacodynamic (PK-PD) modeling to recommend a personalized clopidogrel dosing regimen for individuals with varying CYP2C19 phenotypes and baseline P2Y12 reaction unit (PRU) levels. Data from a prospective phase 1 clinical trial involving 36 healthy male participants were used to develop the populat...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 30, 2023 Category: Drugs & Pharmacology Authors: Yun Seob Jung, Byung Hak Jin, Min Soo Park, Choon Ok Kim, Dongwoo Chae Tags: ARTICLE Source Type: research

Skipping a pillar does not make for strong foundations: Pharmacokinetic ‐pharmacodynamic reasoning behind the shape of dose–response relationships in oncology
AbstractDose –response analysis is often applied to the quantification of drug-effect especially for slowly responding disease end points where a comparison is made across dose levels after a particular period of treatment. It has long been recognized that exposure – response is more appropriate than dose– response. However, trials necessarily are designed as dose–response experiments. Second, a wide range of functional forms are used to express relationships between dose and response. These considerations are also important for clinical development because pharmacokinetic (PK; and variability) plus pharmacokinetic...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 29, 2023 Category: Drugs & Pharmacology Authors: James W. T. Yates, Hitesh B. Mistry Tags: REVIEW Source Type: research

Tutorial on Model Selection and Validation of Model Input into Precision Dosing Software for Model ‐Informed Precision Dosing
AbstractThere has been rising interest in using model-informed precision dosing to provide personalized medicine to patients at the bedside. This methodology utilizes population pharmacokinetic models, measured drug concentrations from individual patients, pharmacodynamic biomarkers, and Bayesian estimation to estimate pharmacokinetic parameters and predict concentration-time profiles in individual patients. Using these individualized parameter estimates and simulated drug exposure, dosing recommendations can be generated to maximize target attainment to improve beneficial effect and minimize toxicity. However, the accurac...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 29, 2023 Category: Drugs & Pharmacology Authors: Zachary L. Taylor, Ethan A. Poweleit, Kelli Paice, Katherine M. Somers, Kathryn Pavia, Alexander A. Vinks, Nieko Punt, Tomoyuki Mizuno, Sonya Tang Girdwood Tags: TUTORIAL Source Type: research

A Markov model of fibrosis development in Non ‐Alcoholic Fatty Liver Disease predicts fibrosis progression in clinical cohorts
AbstractDisease progression in non-alcoholic steatohepatitis (NASH) is highly heterogenous and remains poorly understood. Fibrosis stage is currently the best predictor for development of end-stage liver disease and mortality. Better understanding and quantifying the impact of factors affecting NASH and fibrosis is essential to inform clinical study design. We developed a population Markov model to describe the transition probability between fibrosis stages and mortality using a unique clinical non-alcoholic fatty liver disease (NAFLD) cohort with serial biopsies over three decades. We evaluated covariate effects on all mo...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 26, 2023 Category: Drugs & Pharmacology Authors: Jane Kn öchel, Linnéa Bergenholm, Eman Ibrahim, Stergios Kechagias, Sara Hansson, Mathias Liljeblad, Patrik Nasr, Björn Carlsson, Mattias Ekstedt, Sebastian Ueckert Tags: ARTICLE Source Type: research

Physiologically Based Mechanistic Insight into Differential Risk of Valproate Hepatotoxicity between Children and Adults: A Focus on Ontogeny Impact
AbstractThe anticonvulsant valproic acid (VPA) despite complex pharmacokinetics has been in clinical use for nearly six decades. Previous reports indicated neonates, infants, and toddlers/preschoolers had higher risk of valproate hepatotoxicity than adults. However, dosing recommendations for those less than ten years of age are lacking. To decipher clinical puzzles, physiologically based pharmacokinetics (PBPK) models of VPA and its hepatotoxic metabolite 4-ene-VPA were constructed and simulated with particularly integrated information of drug-metabolizing enzyme ontogeny. Adult and pediatric PK data of VPA (n  = 143 ...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 22, 2023 Category: Drugs & Pharmacology Authors: Yu ‐Ting Huang, Yen‐Ming Huang, Fan‐Lu Kung, Chun‐June Lin, Tun Jao, Yunn‐Fang Ho Tags: ARTICLE Source Type: research

Association between SARS ‐CoV‐2 viral kinetics and clinical score evolution in hospitalized patients
AbstractThe role of antiviral treatment in COVID-19 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS-2), using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS-2...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 21, 2023 Category: Drugs & Pharmacology Authors: Nad ège Néant, Guillaume Lingas, Alexandre Gaymard, Drifa Belhadi, Maya Hites, Thérèse Staub, Richard Greil, Jose‐Artur Paiva, Julien Poissy, Nathan Peiffer‐Smadja, Dominique Costagliola, Yazdan Yazdanpanah, Maude Bouscambert‐Duchamp Tags: ARTICLE Source Type: research