Plasma concentrations and disposition of clonidine following a constant 14-day epidural infusion in cancer patients

Epidural administration of clonidine, a partial alpha(2)-adrenergic agonist, provides effective relief for patients with intractable cancer pain. However, clonidine's long plasma elimination half-life suggests a potential for plasma accumulation following repeated doses or constant infusion. Adult male and female cancer patients experiencing severe, intractable pain were administered a continuous epidural infusion (30 mu g/h) of clonidine hydrochloride for 14 days. Plasma clonidine concentrations were determined for 31 patients using a radioimmunoassay with a limit of quantitation of 0.062 ng/mL. Mean (+/- SD) plasma clonidine concentration and calculated total body clearance after 7 days of infusion (respectively, 2.19 +/- 1.17 ng/mL, n = 24; 279 +/- 184 mL/min, n = 27) were comparable to those following 14 days of infusion (2.50 +/- 1.51 ng/mL, n = 19; 272 +/- 163 mL/min, n = 21). Clonidine does not appear to accumulate in the plasma compartment during prolonged (14-day) continuous epidural infusion in cancer patients.