Modeling Drug Absorption from the Dermis after an Injection.

Area of Science:

• Pharmacokinetics
• Biomedical Engineering
• Dermal Drug Delivery

Background:

• Previous models estimated dermal absorption based on molecular size and protein binding.
• Steady-state models assumed constant lymphatic flow and two-pore theory for blood absorption.
• Limitations existed in predicting absorption dynamics immediately post-injection.

Purpose of the Study:

• To develop an unsteady-state dermal absorption model for immediate post-injection scenarios.
• To incorporate time-varying pressure gradients caused by intradermal injections.
• To improve the prediction of absorption rate constants for small and macromolecules.

Main Methods:

• Developed a new model building on steady-state concepts for unsteady-state conditions.
• Incorporated time-dependent blood absorption via two-pore theory.
• Modeled lymphatic absorption considering valve dynamics and pressure-driven flow.

Main Results:

• The unsteady-state model accurately predicts experimental absorption rate constants.
• Accounting for localized, time-varying pressure significantly improves absorption predictions.
• The model demonstrates improved understanding of macromolecule uptake dynamics.

Conclusions:

• The developed unsteady-state model offers a more accurate prediction of dermal absorption post-injection.
• Time-varying pressure is a critical factor in macromolecule uptake from dermal interstitial fluid.
• This work advances the understanding of drug delivery and absorption following intradermal administration.