Related Experiment Video
Updated: Jul 12, 2025
08:27
Design and Validation of a Volumetric-extrusion Bioprinter for Bioprinting of Soluble Basement Membrane Extract for Translational Research
Published on: March 28, 2025
225
.
Makiko Shimizu1, Shotaro Uehara2, Katsuhiro Ohyama3
1Lab. of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Japan.
Drug Metabolism and Disposition: the Biological Fate of Chemicals
|October 25, 2023
Summary
This study developed pharmacokinetic models to predict atomoxetine levels in children. A metabolite ratio may help identify CYP2D6 intermediate metabolizers for optimized ADHD treatment.
Area of Science:
- Pharmacology
- Pharmacokinetics
- Drug Metabolism
Background:
- Atomoxetine is an ADHD medication and a CYP2D6 probe substrate.
- Drug interactions and individual metabolic differences impact atomoxetine efficacy and safety.
- Accurate dosing requires understanding CYP2D6 enzyme activity.
Purpose of the Study:
- To develop and validate human physiologically based pharmacokinetic (PBPK) models for atomoxetine in pediatric patients.
- To investigate drug interactions between atomoxetine and paroxetine using humanized-liver mouse models.
- To identify simple methods for determining CYP2D6 phenotypes in pediatric populations.
Main Methods:
- Utilized humanized-liver mouse studies to observe drug interactions.
- Established human PBPK models by scaling up mouse data.
- Validated models against drug monitoring data from Japanese pediatric participants (8-14 years).
Main Results:
- PBPK models accurately predicted atomoxetine and its metabolite concentrations in pediatric patients.
- High hepatic exposure in potential intermediate metabolizers (CYP2D6*10, *36 alleles) may explain adverse effects.
- A narrow ratio of 4-hydroxyatomoxetine to N-desmethylatomoxetine may indicate CYP2D6 intermediate metabolizers.
Conclusions:
- Validated pharmacokinetic models can predict atomoxetine steady-state concentrations in children.
- A simple metabolite ratio in urine/plasma could serve as a semi-quantitative marker for CYP2D6 intermediate metabolizers.
- This approach may aid in optimizing atomoxetine dosage and evaluating clinical outcomes.
Related Concept Videos
01:23Design of Prismatic Beams for Bending
243
The design of prismatic beams, structural elements with a uniform cross-section, focuses on ensuring safety and structural integrity under load. The design process begins by determining the allowable stress, either from material properties tables, or by dividing the material's ultimate strength by a safety factor. This safety factor is essential for accommodating uncertainties, and varies depending on the material—timber, steel, or concrete—with each having unique strength and...
243
01:16Cell Motility through Blebbing
1.9K
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Blebbing Through the Matrix
In multicellular...
1.9K
01:10Bending
287
Pure bending is a fundamental concept in structural mechanics, essential for understanding how materials deform under symmetrical loads without direct forces. Pure bending occurs when prismatic members, such as beams, are subjected to equal and opposite moments that induce bending. The phenomenon is crucial as it allows for predicting stress distributions without the influence of axial or shear forces.
In pure bending, the bending stress in a beam is calculated based on the bending moment and...
In pure bending, the bending stress in a beam is calculated based on the bending moment and...
287
01:30Bending Moment Diagram
1.2K
A bending moment diagram is a graphical representation of the bending moments experienced by a beam under load along the beam length. It is an essential tool for engineers and designers to analyze structures and ensure they can withstand applied forces. The steps to create the bending moment diagram for a beam are listed below.
Determine reactive forces and couple moments: Calculate all the reactive forces and couple moments acting on the beam. In certain cases, when the beam is inclined at an...
Determine reactive forces and couple moments: Calculate all the reactive forces and couple moments acting on the beam. In certain cases, when the beam is inclined at an...
1.2K
01:39Anaphase A and B
4.1K
Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
4.1K
01:07Symmetric Member in Bending
173
In the study of the mechanics of materials, analyzing the behavior of prismatic members under opposing couples is crucial for understanding internal stress distributions, which are essential for structural design. When subjected to couples, a prismatic member experiences internal forces that maintain equilibrium. A couple, characterized by two equal and opposite forces, creates a moment but no resultant force. The internal forces at any section cut of the member must balance these external...
173