Journal of Pharmacokinetics and Pharmacodynamics 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.

Evaluation of ChatGPT and Gemini large language models for pharmacometrics with NONMEM
AbstractTo assess ChatGPT 4.0 (ChatGPT) and Gemini Ultra 1.0 (Gemini) large language models on NONMEM coding tasks relevant to pharmacometrics and clinical pharmacology. ChatGPT and Gemini were assessed on tasks mimicking real-world applications of NONMEM. The tasks ranged from providing a curriculum for learning NONMEM, an overview of NONMEM code structure to generating code. Prompts in lay language to elicit NONMEM code for a linear pharmacokinetic (PK) model with oral administration and a more complex model with two parallel first-order absorption mechanisms were investigated. Reproducibility and the impact of “temper...
Source: Journal of Pharmacokinetics and Pharmacodynamics - April 24, 2024 Category: Drugs & Pharmacology Source Type: research

Target-mediated drug disposition model for drugs with N   & gt;  2 binding sites that bind to a target with one binding site
AbstractThe paper extended the TMDD model to drugs with more than two (N >  2) identical binding sites (N-to-one TMDD). The quasi-steady-state (N-to-one QSS), quasi-equilibrium (N-to-one QE), irreversible binding (N-to-one IB), and Michaelis–Menten (N-to-one MM) approximations of the model were derived. To illustrate properties of new equations and approximations,N = 4 case was investigated numerically. Using simulations, the N-to-one QSS approximation was compared with the full N-to-one TMDD model. As expected, and similarly to the standard TMDD for monoclonal antibodies (mAb), N-to-one QSS predictions were n...
Source: Journal of Pharmacokinetics and Pharmacodynamics - April 19, 2024 Category: Drugs & Pharmacology Source Type: research

A systematic evaluation of population pharmacokinetic models for polymyxin B in patients with liver and/or kidney dysfunction
This study aimed to systemically evaluate eleven PMB PopPK models from ten published literature based on a new independent population, which was divided into four different populations, patients with liver dysfunction, kidney dysfunction, liver and kidney dysfunction, and normal liver and kidney function. The whole data set consisted of 146 patients with 391 PMB concentrations. The prediction- and simulation-based diagnostics and Bayesian forecasting were conducted to evaluate model predictability. In the overall evaluation process, none of the models exhibited satisfactory predictive ability in both prediction- and simula...
Source: Journal of Pharmacokinetics and Pharmacodynamics - April 16, 2024 Category: Drugs & Pharmacology Source Type: research

Five multivariate Duchenne muscular dystrophy progression models bridging six-minute walk distance and MRI relaxometry of leg muscles
AbstractThe study aimed to provide quantitative information on the utilization of MRI transverse relaxation time constant (MRI-T2) of leg muscles in DMD clinical trials by developing multivariate disease progression models of Duchenne muscular dystrophy (DMD) using 6-min walk distance (6MWD) and MRI-T2. Clinical data were collected from the prospective and longitudinalImagingNMD study. Disease progression models were developed by a nonlinear mixed-effect modeling approach. Univariate models of 6MWD and MRI-T2 of five muscles were developed separately. Age at assessment was the time metric. Multivariate models were develope...
Source: Journal of Pharmacokinetics and Pharmacodynamics - April 12, 2024 Category: Drugs & Pharmacology Source Type: research

Impact of covariate model building methods on their clinical relevance evaluation in population pharmacokinetic analyses: comparison of the full model, stepwise covariate model (SCM) and SCM+ approaches
This study must be extended to other methods and completed by a more complex high-dimensional simulation framework. (Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - April 9, 2024 Category: Drugs & Pharmacology Source Type: research

Model-based comparison of subcutaneous versus sublingual apomorphine administration in the treatment of motor fluctuations in Parkinson ’s disease
The objective of this study was to compare the effectiveness of subcutaneous (SC) and sublingual (SL) formulations of apomorphine for the treatment of motor fluctuations in Parkinson ’s disease using a pharmacokinetics (PK)/pharmacodynamics (PD) modeling approach. The PK of SC and SL apomorphine are best described by a one-compartment model with first-order absorption and a two-compartment model with delayed absorption, respectively. The PK/PD model relating apomorphine plasma concentrations to the Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores was described by a sigmoidal Emax model assuming effective c...
Source: Journal of Pharmacokinetics and Pharmacodynamics - April 5, 2024 Category: Drugs & Pharmacology Source Type: research

Docetaxel, cyclophosphamide, and epirubicin: application of PBPK modeling to gain new insights for drug-drug interactions
In conclusion, the PBPK models can be used to further investigate the DDI potential of each drug and to develop dosage recommendations for concurrent usage by additional perpetrators or victims.Graphical abstract (Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 30, 2024 Category: Drugs & Pharmacology Source Type: research

Longitudinal modeling of efficacy response in patients with lupus nephritis receiving belimumab
In conclusion, the 10 mg/kg IV dose was considered appropriate in all patients and there was no evidence to suggest a hig her response would be achieved by increasing the dose. (Source: Journal of Pharmacokinetics and Pharmacodynamics)
Source: Journal of Pharmacokinetics and Pharmacodynamics - March 29, 2024 Category: Drugs & Pharmacology Source Type: research