Dural permeability to narcotics: in vitro determination and application to extradural administration

Area of Science:

• Pharmacology
• Neuroscience
• Biophysics

Background:

• The dura mater, a protective membrane surrounding the brain and spinal cord, acts as a barrier to substance passage.
• Understanding dural permeability is crucial for drug delivery to the central nervous system.

Purpose of the Study:

• To quantify the in vitro permeability of cranial and lumbar dura to various substances.
• To investigate the relationship between molecular weight and drug diffusion across the dura.
• To develop a model for predicting dural drug transfer, particularly for narcotic analgesics.

Main Methods:

• In vitro measurement of dura mater permeability using postmortem human tissue.
• Analysis of permeability in relation to molecular weight and diffusion processes.
• Calculation of differential mass selectivity coefficients for lumbar and cranial dura.

Main Results:

• Dural permeability showed a linear inverse relationship with the square root of molecular weight, consistent with diffusion.
• Differential mass selectivity coefficients were similar for cranial (0.9) and lumbar (0.8) dura.
• Diffusion rates were higher than in simple liquids but lower than in lipid membranes, suggesting thickness as the primary barrier.

Conclusions:

• Dural permeability is primarily governed by its thickness rather than inherent impermeability.
• Drug molecular weight and absorption rate are key factors influencing dural transfer efficiency.
• Low molecular weight and slow absorption enhance drug transfer across the dura, with potential for significant differences in narcotic transfer.