- -

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

RiuNet: Institutional repository of the Polithecnic University of Valencia

Share/Send to

Cited by

Statistics

  • Estadisticas de Uso

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

Show simple item record

Files in this item

dc.contributor.author Reig-López, Javier es_ES
dc.contributor.author M. Cuquerella-Gilabert es_ES
dc.contributor.author Bandín-Vilar, Enrique es_ES
dc.contributor.author Merino-Sanjuán, Matilde es_ES
dc.contributor.author Mangas-Sanjuán, Victor es_ES
dc.contributor.author García-Arieta, Alfredo es_ES
dc.date.accessioned 2024-07-30T18:04:33Z
dc.date.available 2024-07-30T18:04:33Z
dc.date.issued 2024-06 es_ES
dc.identifier.issn 0939-6411 es_ES
dc.identifier.uri http://hdl.handle.net/10251/206887
dc.description.abstract [EN] 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 (R). 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. es_ES
dc.language Inglés es_ES
dc.publisher Elsevier es_ES
dc.relation.ispartof European Journal of Pharmaceutics and Biopharmaceutics es_ES
dc.rights Reconocimiento - No comercial (by-nc) es_ES
dc.subject Bioequivalence es_ES
dc.subject Ibuprofen es_ES
dc.subject PBPK es_ES
dc.subject Racemase es_ES
dc.subject Stereoselectivity es_ES
dc.title Bioequivalence risk assessment of oral formulations containing racemic ibuprofen through a chiral physiologically based pharmacokinetic model of ibuprofen enantiomers es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1016/j.ejpb.2024.114293 es_ES
dc.rights.accessRights Abierto es_ES
dc.description.bibliographicCitation Reig-López, J.; M. Cuquerella-Gilabert; Bandín-Vilar, E.; Merino-Sanjuán, M.; Mangas-Sanjuán, V.; García-Arieta, A. (2024). Bioequivalence risk assessment of oral formulations containing racemic ibuprofen through a chiral physiologically based pharmacokinetic model of ibuprofen enantiomers. European Journal of Pharmaceutics and Biopharmaceutics. 199. https://doi.org/10.1016/j.ejpb.2024.114293 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1016/j.ejpb.2024.114293 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 199 es_ES
dc.identifier.pmid 38641229 es_ES
dc.relation.pasarela S\523073 es_ES


This item appears in the following Collection(s)

Show simple item record