eprintid: 14361 rev_number: 8 eprint_status: archive userid: 2 dir: disk0/00/01/43/61 datestamp: 2024-09-24 23:30:09 lastmod: 2024-09-24 23:30:10 status_changed: 2024-09-24 23:30:09 type: article metadata_visibility: show creators_name: Yousef, Malaz creators_name: Yáñez, Jaime A. creators_name: Löbenberg, Raimar creators_name: Davies, Neal M. creators_id: creators_id: jaime.yanez@unini.edu.mx creators_id: creators_id: title: Upholding or Breaking the Law of Superposition in Pharmacokinetics ispublished: pub subjects: uneat_bm divisions: uninimx_produccion_cientifica full_text_status: public keywords: pharmacokinetics; superposition; steady state; linearity; multiple dosing abstract: The law of superposition underpins first-order linear pharmacokinetic relationships. Most drugs, therefore, after a single dose can be described by first-order or linear processes, which can be superposed to understand multiple-dose regimen behavior. However, there are a number of situations where drugs could display behaviors after multiple dosing that leads to capacity-limited or saturation non-linear kinetics and the law of superposition is overruled. This review presents a practical guide to understand the equations and calculations for single and multiple-dosing regimens after intravenous and oral administration. It also provides the pharmaceutical basis for saturation in ADME processes and the consequent changes in the area under the concentration–time curve, which represents drug exposure that can lead to the modulation of efficacy and/or toxic effects. The pharmacokineticist must implicitly understand the principles of superposition, which are a central tenet of drug behavior and disposition during drug development. date: 2024 publication: Biomedicines volume: 12 number: 8 pagerange: 1843 id_number: doi:10.3390/biomedicines12081843 refereed: TRUE issn: 2227-9059 official_url: http://doi.org/10.3390/biomedicines12081843 access: open language: en citation: Artículo Materias > Biomedicina Universidad Internacional Iberoamericana México > Investigación > Artículos y libros Abierto Inglés The law of superposition underpins first-order linear pharmacokinetic relationships. Most drugs, therefore, after a single dose can be described by first-order or linear processes, which can be superposed to understand multiple-dose regimen behavior. However, there are a number of situations where drugs could display behaviors after multiple dosing that leads to capacity-limited or saturation non-linear kinetics and the law of superposition is overruled. This review presents a practical guide to understand the equations and calculations for single and multiple-dosing regimens after intravenous and oral administration. It also provides the pharmaceutical basis for saturation in ADME processes and the consequent changes in the area under the concentration–time curve, which represents drug exposure that can lead to the modulation of efficacy and/or toxic effects. The pharmacokineticist must implicitly understand the principles of superposition, which are a central tenet of drug behavior and disposition during drug development. metadata Yousef, Malaz; Yáñez, Jaime A.; Löbenberg, Raimar y Davies, Neal M. mail SIN ESPECIFICAR, jaime.yanez@unini.edu.mx, SIN ESPECIFICAR, SIN ESPECIFICAR (2024) Upholding or Breaking the Law of Superposition in Pharmacokinetics. Biomedicines, 12 (8). p. 1843. ISSN 2227-9059 document_url: http://repositorio.unini.edu.mx/id/eprint/14361/1/biomedicines-12-01843.pdf