Efficacy and Safety of Mydriatic Microdrops for Retinopathy of Prematurity Screening: The MyMiROPS Randomized Clinical Trial.

Importance: Commercial mydriatics administered in preterm infants during retinopathy of prematurity (ROP) screening have been associated with various cardiorespiratory and gastrointestinal adverse events.

Objective: To examine whether microdrops of a combined mixture of 1.67% phenylephrine and 0.

A Meta-Analysis Methodology in Stan to Estimate Population Pharmacokinetic Parameters from Multiple Aggregate Concentration-Time Datasets: Application to Gevokizumab mPBPK Model.

The aim of the present study was to develop and evaluate the performance of a methodology to estimate the population pharmacokinetic (PK) parameters along with the inter-individual variabilities (IIVs) from patients' reported aggregate concentration-time data, in particular, mean plasma concentrations and their standard deviations (SDs) versus time, such as those often found in published graphs. This method was applied to the published data of gevokizumab, a novel monoclonal anti-interleukin-1β antibody, in order to estimate the drug's population pharmacokinetic (PopPK) parameters of a second-generation minimal physiologically based pharmacokinetic (mPBPK) model. Assuming this mPBPK model, a mixed effects approach was utilized to allow accounting for the random inter-group variability (IGV) that was assumed among different dosage groups.

Simulating realistic patient profiles from pharmacokinetic models by a machine learning postprocessing correction of residual variability.

We address the problem of model misspecification in population pharmacokinetics (PopPK), by modeling residual unexplained variability (RUV) by machine learning (ML) methods in a postprocessing step after conventional model building. The practical purpose of the method is the generation of realistic virtual patient profiles and the quantification of the extent of model misspecification, by introducing an appropriate metric, to be used as an additional diagnostic of model quality. The proposed methodology consists of the following steps: After developing a PopPK model, the individual residual errors IRES = DV-IPRED, are computed, where DV are the observations and IPRED the individual predictions and are modeled by ML to obtain IRES.

Extrapolation of lung pharmacokinetics of antitubercular drugs from preclinical species to humans using PBPK modelling.

Objectives: To develop physiologically based pharmacokinetic (PBPK) models for widely used anti-TB drugs, namely rifampicin, pyrazinamide, isoniazid, ethambutol and moxifloxacin lung pharmacokinetics (PK)-regarding both healthy and TB-infected tissue (cellular lesion and caseum)-in preclinical species and to extrapolate to humans.

Methods: Empirical models were used for the plasma PK of each species, which were connected to multicompartment permeability-limited lung models within a middle-out PBPK approach with an appropriate physiological parameterization that was scalable across species. Lung's extracellular water (EW) was assumed to be the linking component between healthy and infected tissue, while passive diffusion was assumed for the drug transferring between cellular lesion and caseum.

Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice.

Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the nasal cavity with the central nervous system (CNS) is based on two nerves: olfactory and trigeminal. Moreover, the high vasculature of the respiratory area enables systemic absorption avoiding possible hepatic metabolism.