Personalized Secukinumab Treatment in Patients with Plaque Psoriasis Using Model-Informed Precision Dosing.

Patient care and control of inflammatory disorders, such as psoriasis, can be improved by model-informed precision dosing (MIPD) techniques based on population pharmacokinetic/pharmacodynamic (PK/PD) models. Clinical dose selection decisions based on MIPD strategies need to take account of the uncertainty associated with the individual PK/PD model parameters, which is determined by the quantity of individual observational data collected in clinical practice. The aim of this study was to propose an approach for personalized dosage regimens of secukinumab (SCK) in 22 Spanish patients with plaque psoriasis, whose severity level was considered moderate to severe, taking into account the uncertainty associated with individual parameters in a population-based PK/PD model.

Model-Informed Precision Dosing for Personalized Ustekinumab Treatment in Plaque Psoriasis.

Background/objectives: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, the extent of individual experimental data gathered during MIPD significantly influences the uncertainty in estimating individual PK/PD parameters, affecting clinical dose selection decisions.

Methods: This study proposes a methodology to individualize ustekinumab (UTK) dosing strategies for 23 Spanish patients with moderate to severe chronic plaque psoriasis.

Impact of Time on Parameters for Assessing the Microstructure Equivalence of Topical Products: Diclofenac 1% Emulsion as a Case Study.

The demonstration of bioequivalence proposed in the European Medicines Agency's (EMA's) draft guideline for topical products with the same qualitative and quantitative composition requires the confirmation of the internal structure equivalence. The impact of the shelf-life on the parameters proposed for internal structure comparison has not been studied. The objectives of this work were: (1) to quantify the effect of the time since manufacturing on the mean value and variability of the parameters proposed by the EMA to characterize the internal structure and performance of topical formulations of a complex topical formulation, and (2) to evaluate the impact of these changes on the assessment of the microstructure equivalence.

Bioequivalence risk assessment of oral formulations containing racemic ibuprofen through a chiral physiologically based pharmacokinetic model of ibuprofen enantiomers.

The characterization of the time course of ibuprofen enantiomers can be useful in the selection of the most sensitive analyte in bioequivalence studies. Physiologically based pharmacokinetic (PBPK) modelling and simulation represents the most efficient methodology to virtually assess bioequivalence outcomes. In this work, we aim to develop and verify a PBPK model for ibuprofen enantiomers administered as a racemic mixture with different immediate release dosage forms to anticipate bioequivalence outcomes based on different particle size distributions.

Phys-DAT: A physiologically-based pharmacokinetic model for unraveling the dissolution, transit and absorption processes using PhysPK®.

Background And Objective: In silico methods have become the key for efficiently testing and qualifying drug properties. Due to the complexity of the LADME processes and drug characteristics associated to oral drug absorption, there is a growing demand in the development of Physiologically-based Pharmacokinetic (PBPK) software with greater flexibility. Thus, the aims of this work are (i) to develop a mechanistic-based modeling framework of dissolution, transit and absorption (Phys-DAT) processes in the PhysPK platform and (ii) to assess the predictive power of the acausal MOOM methodology embedded in Phys-DAT versus reference ODE-based PBPK software.