Characterization of neonatal and infant enterostomy fluids

Waal, Tom de; Brouwers, Joachim; Mols, Raf; Hoffman, Ilse; Rayyan, Maissa; Augustijns, Patrick

doi:10.1016/j.ijpharm.2023.122943

Cited by 5 publications

(5 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For all explored characteristics, the variability was larger in infant HIF compared to adult HIF. The high variability, in line with previous reports 19,23 , could partly be attributed to the non-controlled feeding conditions in the infant patients in contrast to the adult volunteers, who received a standardized meal prior to fluid collection.…”

Section: The Comparison In Tablesupporting

confidence: 88%

“…In all patients, multiple enterostomy fluid samples were collected during a period of 1 to 16 weeks. The collection and characterization of these distinct samples have been thoroughly discussed in a previous study 23 .…”

Section: Intestinal Fluid Poolsmentioning

confidence: 99%

“…Both the aqueous and total fractions of each adult and infant HIF pool were characterized with respect to pH, buffer capacity, osmolality, total protein, bile salts, phospholipids, and lipid digestion products, following the previously described methodology 23 .…”

Section: Characterization Of Intestinal Fluid Poolsmentioning

confidence: 99%

“…In this respect, we recently collected intestinal enterostomy fluids from neonatal and infant patients (further referred to as infant HIF) and characterized these fluids with respect to factors that may affect intestinal drug absorption (i.e., pH, buffer capacity, osmolality, total protein, bile salts, phospholipids and lipids) 23 . For some factors, average values in infant HIF substantially differed from previously reported values in adult HIF 24,25 .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Characterization of neonatal and infant enterostomy fluids - part II: Drug solubility

Waal

Brouwers

Rayyan

et al. 2023

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Section: The Comparison In Tablesupporting

confidence: 88%

Section: Intestinal Fluid Poolsmentioning

confidence: 99%

Section: Characterization Of Intestinal Fluid Poolsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of neonatal and infant enterostomy fluids - part II: Drug solubility

Waal

Brouwers

Rayyan

et al. 2023

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

“…Secondly, as a lower bile salt secretion is observed for younger children [ 50 , 51 ], the impact of a decreased bile salt concentration on tacrolimus exposure was explored using the DLM. As can be seen in Supplementary Table S6 , using the ½ FaSSIF and FaSSIF solubility, the prediction of PK parameters was mostly unaffected.…”

Section: Resultsmentioning

confidence: 99%

Investigating Tacrolimus Disposition in Paediatric Patients with a Physiologically Based Pharmacokinetic Model Incorporating CYP3A4 Ontogeny, Mechanistic Absorption and Red Blood Cell Binding

Van der Veken,

Brouwers,

Ozbey

et al. 2023

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Tacrolimus is a crucial immunosuppressant for organ transplant patients, requiring therapeutic drug monitoring due to its variable exposure after oral intake. Physiologically based pharmacokinetic (PBPK) modelling has provided insights into tacrolimus disposition in adults but has limited application in paediatrics. This study investigated age dependency in tacrolimus exposure at the levels of absorption, metabolism, and distribution. Based on the literature data, a PBPK model was developed to predict tacrolimus exposure in adults after intravenous and oral administration. This model was then extrapolated to the paediatric population, using a unique reference dataset of kidney transplant patients. Selecting adequate ontogeny profiles for hepatic and intestinal CYP3A4 appeared critical to using the model in children. The best model performance was achieved by using the Upreti ontogeny in both the liver and intestines. To mechanistically evaluate the impact of absorption on tacrolimus exposure, biorelevant in vitro solubility and dissolution data were obtained. A relatively fast and complete release of tacrolimus from its amorphous formulation was observed when mimicking adult or paediatric dissolution conditions (dose, fluid volume). In both the adult and paediatric PBPK models, the in vitro dissolution profiles could be adequately substituted by diffusion-layer-based dissolution modelling. At the level of distribution, sensitivity analysis suggested that differences in blood plasma partitioning of tacrolimus may contribute to the variability in exposure in paediatric patients.

show abstract