Cerebrospinal Fluid and Plasma Concentrations of Clonidine in Pigs after Epidural, Intravenous and Intramuscular Administration

Abstract

Epidural clonidine is an alternate way to treat severe pain in man. The cerebrospinal fluid (CSF) and plasma concentrations resulting after epidural, intravenous (i.v) or intramuscular (i.m.) clonidine, 3 .mu.g/kg b.w. have been determined by a sensitive gas chromatographic method. A porcine model was used, where the epidural and intrathecal spaces were cannulated via the atlanto-occipital membrane. After epidural administration of clonidine the CSF concentrations were maximal 20 minutes after the injection, 129 .+-. 24 ng/ml (mean .+-. S.D.). Clonidine was eliminated from CSF with an apparent half-life of 26 .+-. 8.2 minutes (mean .+-. S.D.). The plasma concentrations stayed below 1 ng/ml. Low plasma and undetectable CSF concentrations resulted after i.v. clonidine. Thus, epidural clonidine readily penetrates the dura mater into the CSF, and there is a marked gradient between CSF and plasma.