Individualized Absorption Models in Population Pharmacokinetic Analyses

• Published in: CPT: pharmacometrics and systems pharmacology Vol. 9; no. 6; pp. 307 - 309
• Main Authors: Jaber, Mutaz M., Al‐Kofahi, Mahmoud, Sarafoglou, Kyriakie, Brundage, Richard C.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2020; John Wiley and Sons Inc; Wiley
• Subjects: Drug dosages; Estimates; Hyperplasia; Pharmacokinetics; Population
• ISSN: 2163-8306; 2163-8306
• DOI: 10.1002/psp4.12513

[...]one cannot always ignore early exposures and there are examples when the absorption process is associated with clinical outcomes. 1–3 In such cases, it is necessary to have an appropriate study design to collect samples when they make a difference, have an absorption model that reasonably reflects those observations, and have an outcome model that links early exposure to outcome. In this perspective, we wish to provide an example to illustrate differences seen when prespecifying the absorption model for each individual by visual inspection of the data from a cohort of children with congenital adrenal hyperplasia being treated with hydrocortisone. Observed concentration‐time profile for three representative subjects, each demonstrating a different absorption shape: first order process (green), an Erlang absorption process (red), and shoulder model for simultaneous distributed‐delay and first‐order processes (blue). Because this is not a formal simulation study, the degree of bias and imprecision that exists in the estimates cannot be commented on.