A method for rapidly predicting drug tissue distribution using surfactant vesicle electrokinetic chromatography

Area of Science:

• Pharmacokinetics
• Analytical Chemistry
• Drug Delivery

Background:

• Inhaled drug distribution in lung tissue is crucial for efficacy and minimizing systemic exposure.
• Lung's unique diffusion characteristics mean tissue and protein binding significantly influence drug distribution.
• Predicting tissue distribution is vital for optimizing inhaled therapeutics.

Purpose of the Study:

• To develop and validate surfactant vesicle electrokinetic chromatography (SEKC) methods for predicting inhaled drug tissue distribution.
• To compare SEKC with other chromatographic techniques for profiling inhaled drug distribution.
• To establish correlations between chromatographic retention and in vivo drug distribution parameters.

Main Methods:

• Development and evaluation of several electrokinetic chromatography methods, including immobilised artificial membrane chromatography.
• Optimization of the docusate sodium salt (AOT) SEKC system for reproducibility, run time, and selectivity.
• Comparison of AOT SEKC retention with in vivo volume of distribution (V(ss)) and tissue-to-plasma water partitioning coefficients (K(pu)).

Main Results:

• The AOT-SEKC system demonstrated excellent reproducibility, short run times, and high selectivity for test compounds.
• A significant correlation was found between AOT SEKC retention and V(ss) for inhaled drugs, irrespective of plasma protein binding.
• Stronger correlations were observed between AOT SEKC retention and lung K(pu) for basic drugs, with the weakest correlation for brain tissue.

Conclusions:

• AOT-SEKC is a valuable high-throughput method for predicting inhaled drug distribution in lung tissue.
• The method effectively correlates with lung tissue partitioning, offering insights into drug behavior in vivo.
• SEKC provides a promising tool for optimizing inhaled drug development by predicting tissue distribution profiles.