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.

Model ‐based assessment of neutrophil‐mediated phagocytosis and digestion of bacteria across in vitro and in vivo studies
AbstractNeutrophil granulocytes are key components of the host response against pathogens, and severe neutropenia, with neutrophil counts below 0.5 ·106 cells/mL, renders patients increasingly vulnerable to infections. Publishedin vitro (n=7) andin vivo (n=5) studies with time-course information on bacterial and neutrophil counts were digitized, to characterize the kinetics of neutrophil-mediated bacterial killing and inform on the immune systems ’ contribution to clearance of bacterial infections. A mathematical model for thein vitro dynamics of bacteria and the kinetics of neutrophil-mediated phagocytosis and digestio...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 13, 2023 Category: Drugs & Pharmacology Authors: Anders Thorsted, Anh Duc Pham, Lena E. Friberg, Elisabet I. Nielsen Tags: ARTICLE Source Type: research

Combining Pharmacometric Models with Predictive and Prognostic Biomarkers for Precision Therapy in Crohn's Disease: A Case Study of Brazikumab
AbstractPharmacometric models were used to investigate the utility of biomarkers in predicting the efficacy (Crohn's Disease Activity Index, CDAI) of brazikumab and provide a data-driven framework for precision therapy for Crohn's disease. In a phase 2a trial in patients with moderate to severe Crohn's disease, treatment with brazikumab, an anti-interleukin 23 monoclonal antibody, was associated with clinical improvement. Brazikumab treatment effect was determined to be dependent on the baseline IL-22 (BIL22) or baseline C-reactive protein (BCRP) (predictive biomarkers), and placebo effect was found to be correlated with t...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 11, 2023 Category: Drugs & Pharmacology Authors: Nan Zhang, Ming Liang Chan, Jing Li, Philip Z. Brohawn, Bo Sun, Inna Vainshtein, Lorin K. Roskos, Raffaella Faggioni, Rada M. Savic Tags: ARTICLE Source Type: research

Optimized infusion rates for N,N ‐dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework
AbstractN,N-dimethyltryptamine (DMT) is a psychedelic compound that is being studied as a therapeutic option in various psychiatric disorders. Due to its short half-life, continuous infusion of DMT has been proposed to extend the psychedelic experience and potential therapeutic effects. The primary aim of this work was to design an infusion protocol for DMT based on a desired level of psychedelic intensity using population pharmacokinetic/pharmacodynamic modeling. As a secondary aim, the impact of choosing a continuous variable or a bounded integer pharmacokinetic/pharmacodynamic model to inform such an infusion protocol w...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 7, 2023 Category: Drugs & Pharmacology Authors: Emma Eckern äs, Jeroen Koomen, Christopher Timmermann, Robin Carhart‐Harris, Daniel Röshammar, Michael Ashton Tags: ARTICLE Source Type: research

Physiologically ‐based pharmacokinetic modeling for investigating the effect of simeprevir on concomitant drugs and an endogenous biomarker of OATP1B
In conclusion, the simeprevir PBPK model developed in this study can quantitatively describe the increase in exposures of concomitant drugs and an endogenous biomarker via inhibition of CYP3A4 and OATP1B. (Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - September 6, 2023 Category: Drugs & Pharmacology Authors: Shinji Nakayama, Kota Toshimoto, Shinji Yamazaki, Jan Snoeys, Yuichi Sugiyama Tags: ARTICLE Source Type: research

How large must a dose ‐optimization trial be?
AbstractRecently promulgated Draft Guidance from the FDA Oncology Center of Excellence recommends randomized, parallel dose-response trials for ‘dose optimization’, but with vaguely stated aims that engage none of the statistical principles which typically attend randomization. Here I advance a criterion for reasonable precision of such trials, and examine its implications for minimum enrollment, within a utility-based framework that ac knowledges interindividual heterogeneity simultaneously in PKPD and in the subjective evaluation of efficacy-toxicity trade-offs. Even when designed and conducted under ideal circumstan...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 5, 2023 Category: Drugs & Pharmacology Authors: David C. Norris Tags: ARTICLE Source Type: research

Evaluation of postprandial total triglycerides within the TIGG model for characterizing postprandial response of glucose, insulin, and GLP ‐1
AbstractThe TIGG model is the first model to integrate glucose and insulin regulation, incretin effect, and triglyceride (TG) response in the lipoprotein subclasses of chylomicrons and VLDL-V6. This model described the response following a high-fat meal in individuals who are lean, obese, and very obese and provided insights into the possible regulation of glucose homeostasis in the extended period following a meal. Often, total TGs are analyzed within clinical studies, instead of lipoprotein subclasses. We extended the existing TIGG model to capture the observed total TGs and determined if this model could be used to pred...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 5, 2023 Category: Drugs & Pharmacology Authors: Jennifer Leohr, Maria C. Kjellsson Tags: ARTICLE Source Type: research

Mid ‐dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients
This study aimed to evaluate the association between polymyxin B (PMB) exposure and acute kidney injury (AKI) and analyze the risk factors for PMB-induced AKI in critically ill patients. Plasma concentrations of PMB were determined using an ultra-performance liquid chromatography-tandem mass spectrometer in intensive care unit patients who were administered PMB. Univariate and multivariate analyses were conducted to identify risk factors. A receiver operating characteristic curve was constructed to assess the discriminant power of the factors and to identify the cut-off value for AKI. The white blood cell count and estimat...
Source: CPT: Pharmacometrics and Systems Pharmacology - September 2, 2023 Category: Drugs & Pharmacology Authors: Jing Wang, Yuanchen Li, Siqi Huang, Min Wang, Lu Jin, Xuemei Luo, Xiaoliang Cheng, Na Yang, Huaijun Zhu Tags: ARTICLE Source Type: research

A comprehensive evaluation in clinic and physiologically ‐based pharmacokinetic modeling and simulation to confirm lack of cytochrome P450–mediated drug–drug interaction potential for pomotrelvir
AbstractPomotrelvir is a new chemical entity and potent direct-acting antiviral inhibitor of the main protease of coronaviruses. Here the cytochrome P450 (CYP) –mediated drug–drug interaction (DDI) potential of pomotrelvir was evaluated for major CYP isoforms, starting with in 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 (b.i.d.) of pomotrelvir, including pomotrelvir coadministration with ritonavir (strong inhibitor of CYP3A4) or midazolam (sensitive substrate of CYP3A4). Furthermor...
Source: CPT: Pharmacometrics and Systems Pharmacology - August 31, 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