Fate of adrenal cortical steroids following intrathecal injection

Abstract

The transfer of adrenal cortical steroids between blood and cerebrospinal fluid has been studied in dogs. Cortisol rapidly reaches equilibrium in the cerebrospinal fluid after intravenous administration. Following the intrathecal injection of cortisol, this steroid leaves the subarachnoid space rapidly, and the increased concentration obtained in the cerebrospinal fluid is transient and dissipated within a few hours after the injection. The intraspinal route of administration of free steroid is, in effect, equivalent to no more than a prolonged intravenous injection-in terms of the concentration of the steroid maintained in cerebrospinal fluid and plasma and the amounts excreted in the urine. The disappearance of a suspension of methylprednisolone acetate in a vehicle which greatly retards the solubility of the steroid and delays its transfer across membranes has also been studied. The possible effects of the vehicle are discussed. The observation that the suspension is only slowly removed from the subarachnoid space is confirmed, and the possible therapeutic implications thereof have been scrutinized. It is concluded that intrathecal administration of adrenal steroids has no pharmacological rationale in demyelinating disease. If steroidal therapy is intended, chronic oral administration is the route of choice.