A Diffusion-Based and Dynamic 3D-Printed Device That Enables Parallel in Vitro Pharmacokinetic Profiling of Molecules

Area of Science:

• Biomedical Engineering
• Pharmacokinetics
• Drug Discovery

Background:

• Preclinical drug development requires accurate determination of drug properties like absorption, distribution, metabolism, and excretion (ADME).
• Existing in vitro systems for pharmacokinetic (PK) profiling have limitations.
• Animal models are traditionally used, but in vitro alternatives are sought.

Purpose of the Study:

• To introduce a novel 3D-printed, diffusion-based, dynamic in vitro device for generating pharmacokinetic (PK) profiles.
• To demonstrate the device's capability in modeling both drug loading and clearance phases.
• To showcase the device's efficiency in terms of sample volume and throughput.

Main Methods:

• A 3D-printed device with six flow channels and integrated porous membrane inserts was designed.
• The device utilizes diffusion across membranes to simulate drug movement.
• Experiments were conducted using fluorescein and levofloxacin, with parameters like flow rate and concentration varied.

Main Results:

• The device successfully generated pharmacokinetic (PK) profiles for fluorescein and levofloxacin.
• A predictive model achieved ~5% coefficient of variation for predicting drug concentrations.
• Analyte depletion followed first-order kinetics, independent of initial concentration.

Conclusions:

• The developed 3D-printed device offers a dynamic and efficient in vitro method for generating pharmacokinetic (PK) profiles.
• It enables simultaneous generation of multiple PK profiles using low sample volumes (milliliter range).
• This technology holds promise for improving preclinical drug assessment and reducing reliance on animal models.