Clonidine is thought to produce analgesia at presynaptic and postjunctional alpha-2-adrenoceptors in the spinal cord by preventing pain signal transmission to the brain.Following a 10 minute intravenous infusion of 300 mcg clonidine HCl to five male volunteers, plasma clonidine levels showed an initial rapid distribution phase (mean ± SD t=9 ± 2 hours) over 24 hours.
The plasma elimination half-life was determined to be 22 ± 15 hours following sample collection for 24 hours. In cerebral spinal fluid (CSF), peak clonidine levels (418 ± 255 ng/m L) were achieved in 26 ± 11 minutes.
The clonidine CSF elimination half-life was 1.3 ± 0.5 hours when samples were collected for 6 hours.
Clonidine hydrochloride is an imidazoline derivative and exists as a mesomeric compound.
The chemical names are Benzenamine,2,6-dichloro-N-2-imidazolidinylidene monohydrochloride and 2-[(2,6-dichlorophenyl) imino]imidazolidine monohydrochloride.
In humans, clonidine metabolism follows minor pathways with the major metabolite, p-hydroxy-clonidine, being present at less than 10% of the concentration of unchanged drug in urine.
The pharmacokinetics of epidurally administered clonidine has not been studied in the pediatric population or in patients with renal or hepatic disease.
The binding of clonidine to plasma protein is primarily to albumin and varies between 20 and 40%.
Epidurally administered clonidine readily partitions into plasma via the epidural veins and attains systemic concentrations (0.5 to 2.0 ng/m L) that are associated with a hypotensive effect mediated by the central nervous system.
In a double-blind, randomized study of cancer patients with severe intractable pain below the C4 dermatome not controlled by morphine, 38 patients were randomized to an epidural infusion of clonidine hydrochloride plus epidural morphine, whereas 47 subjects received epidural placebo plus epidural morphine.