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.

Pharmacometrics enhanced Bayesian borrowing approach to improve clinical trial efficiency: Case of empagliflozin in type 2 diabetes
We report use of a pharmacometrics enhanced Bayesian borrowing (PEBB) approach to leverage historical clinical trial data on a drug product to build models, project the outcome of future clinical trials, and borrow information from these projections to improve the efficiency of future target trials. This design takes a two-stage approach. First, a design phase is performed before target trial data are available to determine the operating characteristics and an appropriate tuning parameter that will be used in the subsequent analysis phase of a chosen target trial. Second, once the target trial data are available, the analy...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 30, 2023 Category: Drugs & Pharmacology Authors: Lucie Fayette, Martin Oliver Sailer, Alejandro Perez ‐Pitarch Tags: ARTICLE Source Type: research

US Food and Drug Administration embraces using innovation to identify optimized dosages for patients with cancer
(Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - August 29, 2023 Category: Drugs & Pharmacology Authors: Stacy S. Shord, Hao Zhu, Jiang Liu, Atiqur Rahman, Brian Booth, Issam Zineh Tags: PERSPECTIVE Source Type: research

Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania
AbstractIvermectin (IVM) is a drug of choice used with albendazole (ALB) for Mass Drug Administration (MDA) to halt transmission of lymphatic filariasis. We investigated IVM pharmacokinetic (PK) variability for its dose optimization during MDA. PK samples were collected at 0, 2, 4 and 6 hours from individuals weighing>  15 Kg (n=468) receiving IVM (3-, 6-, 9-, or 12 mg) and ALB (400 mg) during MDA campaign in Tanzania. Individual characteristics including demographics, laboratory/clinical parameters and pharmacogenetic variations were assessed. IVM plasma concentrations were quantified by LC-MS/MS and analyzed u sing ...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 28, 2023 Category: Drugs & Pharmacology Authors: Adam M. Fimbo, Eulambius M. Mlugu, Eliford Ngaimisi Kitabi, Gerald S. Kulwa, Mohammed A. Iwodyah, Rajabu Hussein Mnkugwe, Peter P. Kunambi, Alpha Malishee, Appolinary A. R. Kamuhabwa, Omary M. Minzi, Eleni Aklillu Tags: ARTICLE Source Type: research

A dynamic model of the intestinal epithelium integrates multiple sources of preclinical data and enables clinical translation of drug ‐induced toxicity.
AbstractWe have built a QST modelling framework focussed on the early prediction of oncotherapeutics-induced clinical intestinal adverse effects. The model describes stem and progenitor cell dynamics in the small intestinal epithelium and integrates heterogeneous epithelial-related processes, such as transcriptional profiles, citrulline kinetics and probability of diarrhea.We fitted a mouse-specific version of the model to quantify doxorubicin and 5-fluorouracil (5-FU) induced toxicity, which included pharmacokinetics and 5-FU metabolism and assumed that both drugs led to cell cycle arrest and apoptosis in stem cells and p...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 25, 2023 Category: Drugs & Pharmacology Authors: Louis Gall, Ferran Jardi, Lieve Lammens, Janet Pi ñero, Terezinha M. Souza, Daniela Rodrigues, Danyel G. J. Jennen, Theo M. de Kok, Luke Coyle, Seung‐Wook Chung, Sofia Ferreira, Heeseung Jo, Kylie. A. Beattie, Colette Kelly, Carrie A. Duc Tags: ARTICLE Source Type: research

A Comprehensive Evaluation in Clinic and PBPK Modeling and Simulation to Confirm Lack of CYP450 Mediated Drug ‐Drug Interaction Potential for Pomotrelvir
AbstractPomotrelvir is a new chemical entity and potent direct-acting antiviral (DAA) inhibitor of the main protease (Mpro) of coronaviruses (CoVs). Here the cytochrome P450 (CYP) -mediated drug-drug interaction (DDI) potential of pomotrelvir was evaluated for major CYP isoforms, starting within vitro assays followed by the basic static model assessment. The identified CYP3A4-mediated potential DDIs were evaluated clinically at a supratherapeutic dose of 1050 mg twice daily (BID) of pomotrelvir, including pomotrelvir co-administration with ritonavir (strong inhibitor of CYP3A4) or midazolam (sensitive substrate of CYP3A4)....
Source: CPT: Pharmacometrics and Systems Pharmacology - August 25, 2023 Category: Drugs & Pharmacology Authors: Ziping Yang, Nathalie Rioux, Ludwig Vincent, Hannah M. Jones, David Cha, Andrew Plummer, David Wilfret, Brian P. Kearney Tags: ARTICLE Source Type: research

SARS ‐CoV‐2 viral dynamic modeling to inform model selection and timing and efficacy of antiviral therapy
In this study, eight published viral dynamic models were assessed, and model selection was performed. Viral load data were collected from a community surveillance study, including 2155 measurements from 162 patients (124 household and 38 non-household contacts). An extended version of the target-cell limited model that includes an eclipse phase and an immune response component that enhances viral clearance described best the data. In general, the parameter estimates showed good precision (relative standard error<10), apart from the death rate of infected cells. The parameter estimates were used to simulate the outcomes ...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 23, 2023 Category: Drugs & Pharmacology Authors: Shengyuan Zhang, Akosua A. Agyeman, Christoforos Hadjichrysanthou, Joseph F. Standing Tags: ARTICLE Source Type: research

Population Pharmacokinetic Analyses for Belzutifan to Inform Dosing Considerations and Labeling
AbstractBelzutifan (Welireg, Merck& Co, Inc.) is an oral, potent inhibitor of hypoxia-inducible factor (HIF) 2 α, approved for the treatment of certain patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, and pancreatic neuroendocrine tumors (pNET). It is primarily metabolized by the polymorphic uridine 5'-diphospho-glucuronosyltransf erase (UGT) 2B17 and cytochrome (CYP) 2C19. A population pharmacokinetic (PK) model was built, using NONMEM® v7.3, based on demographics/PK data from 3 clinical pharmacology (food effect, formulation bridging, genotyp...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 19, 2023 Category: Drugs & Pharmacology Authors: Dhananjay D. Marathe, Petra M. Jauslin, Huub Jan Kleijn, Carolina de Miranda Silva, Anne Chain, Thomas Bateman, Peter M. Shaw, Anson K. Abraham, Eunkyung A. Kauh, Yanfang Liu, Rodolfo F. Perini, Dinesh P. de Alwis, Lokesh Jain Tags: ARTICLE Source Type: research