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This review explains (1) how TMDD happens (2) why large-molecule and small-molecule compounds exhibiting TMDD demonstrate substantially different nonlinear PK behaviors (3) what nonlinear PK profiles look like in large-molecule and small-molecule compounds exhibiting TMDD, using pegfilgrastim, erythropoietin, ABT-384, and linagliptin as case examples and (4) how to identify whether the nonlinear PK of a compound is because of TMDD.ĪBT-384 Target-mediated drug disposition erythropoietin linagliptin nonlinear PK pegfilgrastim. The goal of this review is to serve as a "primer" on TMDD. phoenix winnonlin’s advanced reporting capabilities are very useful when compiling stand-alone pk reports, facilitating rapid illustration of pk data through workflows and templates however, when results are integrated into a large csr, it is often preferable to generate tlfs in sas for consistency with the remainder of the clinical report (e.g.
Phoenix WinNonlin includes a large library of pharmacokinetic, pharmacodynamic, noncompartmen-tal, PK/PD linked, and indirect response models. As the interaction between a drug and its pharmacologic target belongs to the process of pharmacodynamics (PD), TMDD can be viewed as a consequence of "PD affecting PK." Although there are numerous TMDD-related articles in the literature, most of them focus on characterizing TMDD using various mathematical models, which may not be suitable for those readers who have little interest in mathematical modeling and only want to have an understanding of the basic concept. suited for PK/PD modeling and noncompartmental analysis used to evaluate data from bioavailability and clinical pharmacology studies. PHOENIX VERSION 8.Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetic (PK) phenomenon that is caused by high-affinity binding of a compound to its pharmacologic targets. How to set dose and tau in NCA Or making the situation more. Consultation on Experimental Design for PK/PD Correlation and Modeling Analyses. I assume that PK concentration is at steady state at that time points. We collected the blood sample on Day 4 (pre-dose and several time points post-dose) for PK analysis. Consultation services with PK scientists. Drug A was dosed 300 mg on Day 1 and 30 mg on Days 2 to 6. Written interpretation of PK/PD and related statistical analysis results. Regulatory agencies, including the US FDA, Japan Pharmaceutical and Medical Device Agency (PMDA), China Food and Drug Administration (CFDA), and the UK Medicines and Healthcare Products Regulatory Agency (MHRA), all use Phoenix WinNonlin to evaluate drug submissions. Dosing in NCA - posted in Phoenix WNL basics: Hi All, I have a question about the dosing setting in NCA. It is the industry standard for non-compartmental analysis (NCA), pharmacokinetic/pharmacodynamic (PK/PD), and toxicokinetic (TK) modeling with a proven 30-year history. The intermediate PK/PD course will teach you how to set the models in Phoenix WinNonlin and how to interpret the results.
Phoenix WinNonlin is used by over 6,000 scientists at more than 1,500 establishments in 60 countries.
Phoenix WinNonlin™’s integrated tools for data processing, graphing & charting, report generation, and compliance create an efficient, all-in-one collaboration workbench. Certara®, the global leader in model-informed drug development, today announced the launch of its industry-leading PK/PD M&S software, Phoenix 8.1. PK/PD and non-compartmental analyses can be time consuming, requiring detailed attention to every step from data preparation to report generation.