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. A PBPK model incorporating stereoselectivity and non-linearity in plasma protein binding and metabolism as well as R-to-S unidirectional inversion has been developed in Simcyp®. A dataset composed of 11 Phase I clinical trials with 54 scenarios (27 per enantiomer) and 14,452 observations (7129 for R-ibuprofen and 7323 for S-ibuprofen) was used. Prediction errors for AUC0-t and Cmax for both enantiomers fell within the 0.8-1.25 range in 50/54 (93 %) and 42/54 (78 %) of scenarios, respectively. Outstanding model performance, with 10/10 (100 %) of Cmax and 9/10 (90 %) of AUC0-t within the 0.9-1.1 range, was demonstrated for oral suspensions, which strongly supported its use for bioequivalence risk assessment. The deterministic bioequivalence risk assessment has revealed R-ibuprofen as the most sensitive analyte to detect differences in particle size distribution for oral suspensions containing 400 mg of racemic ibuprofen, suggesting that achiral bioanalytical methods would increase type II error and declare non-bioequivalence for formulations that are bioequivalent for the eutomer.

[Addictions to information and communication technologies in Comunitat Valenciana (Spain), 2018-2020]. / Adicciones a las tecnologías de la información y la comunicación en la Comunitat Valenciana, 2018-2020.

OBJECTIVE: To describe the sociodemographic profile of the people treated for addiction to information and communication technologies (ICTs) in the addictive behavior units (ABU) of Comunitat Valenciana, Spain, in 2018-2020. METHOD: Annual analysis and for the global period according to information collected in the ABU records. RESULTS: 219 registered cases, mostly men (87%), under 30 years of age (53%), with primary education or less (51%), and living with parents (57%). In the study period significant changes were observed in age (increase) and employment situation (more active workers). The COVID-19 pandemic's year (2020) accentuated or maintained previous trends. CONCLUSIONS: The person treated for addiction to ICTs in Comunitat Valenciana is mostly male, under 30 years of age and with a primary education level or less, with a trend to increase in age and in proportion of active workers. Prevention should focus on these groups at higher risk.