CSF distribution of opioids in animals and man

The CSF distribution of opioids after subarachnoid administration is important in determining therapeutic and undesirable side‐effects. There are many factors which influence CSF distribution of opioids including the age, position, anatomy of the spinal column of the patient or animal, and the physico‐chemical properties of the opioid solution and of the CSF. Opioids are cleared from their site of administration in CSF by three mechanisms: 1) uptake into the spinal cord, 2) diffusion through the dura and uptake into the blood, and 3) rostral‐caudal CSF distribution. Physico‐chemical factors such as lipid solubility, degree of ionization in the CSF and the baricity of the opioid solution are important in determining the rate of clearance by these three routes. Opioids which are highly lipid soluble, have high affinity for delta and/or kappa opiate receptor subtypes, and are largely non‐ionized at physiologic CSF pH, would have optimal pharmacokinetic properties for subarachnoid administration. These properties would allow administration of a small dose of opioid which would be rapidly taken up into the spinal cord, thereby limiting CSF and vascular distribution to supraspinal brain regions.