Cerebrospinal fluid kinetics of epidural clonidine in man

Ten patients with deafferentation pain after spinal cord injury were given 150 micrograms clonidine epidurally. CSF and plasma samples were collected over the following 24 h, and drug concentrations were measured by radio-immunoassay. The results of only 6 patients are included in the pharmacokinetic analysis because the catheters were not in the epidural space in the remaining 4 patients. These analyses revealed a mean maximum CSF concentration of 228 ng/ml whereas the mean plasma concentration at all time points was less than 0.7 ng/ml. The elimination half-life of epidural clonidine was 66 +/- 2 min, while the absorption half-life was 31 +/- 7 min, Tmax was 60 +/- 7 min and Cmax was 228 +/- 56 ng/ml. The ratio of the area under the curve (AUC) for CSF and plasma was 52. One patient's catheter was intrathecal and 3 were not in the epidural space. The measured plasma concentrations were similar after all injections. As 4 of 6 patients with epidural catheters obtained pain relief and all 3 patients with spasms obtained relief from epidural clonidine, these data suggest that clonidine has a place in the treatment of patients with spinal cord injury.