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

Abstract

The permeability of cranial and lumbar dura to various substances including a number of narcotic analgesics was measured in vitro. Preliminary data On human postmortem material is reported. Permeability had a linear relation to the inverse of the square root of molecular weight. This is the expected relationship for a diffusion process dependent upon molecular weight. The differential mass selectivity coefficients for lumbar and cranial dura were calculated; they were similar at 0.8 and 0.9. This was greater than for diffusion in simple liquids, but much less than that for biological lipid membranes. This suggests that the low rates of diffusion are a property of the thickness of the dura rather than any inherent impermeability. A simple model for the dural transfer of drugs is described, and applied to narcotics. Its purposes were to suggest: the factors involved in the dural transfer of drugs; the physicochemical properties of drugs relevant to their dural transfer; worthwhile measurements in future studies. The model indicates that drug molecular weight and rate of absorption are important determinants of the efficiency of dural transfer. Low molecular weight and slow absorption produce high dural transfers. When applied to narcotics, these factors could produce a difference of up to an order of magnitude in the amount transferred directly across the dura.