Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine

The kinetics of the disposition of intravenous and oral clonidine in five normotensive subjects have been determined. It is proposed that a two-compartment model adequately describes the disposition of the drug. The drug is rapidly distributed (t1/2alpha = 10.8 +/- 4.7 min) but slowly elimainated (t1/2beta = 8.5 +/- 0.9 hr). The bioavailability of oral clonidine in the tablets tested averaged 75.2% and 40 to 50% of the bioavailable dose is excreted unchanged in urine. Renal clearance of the drug showed considerable intersubject variation (1.82 +/- 0.34 ml/min/kg) and exceed the calculated glomerular filtration rate in some subjects. Oral and intravenous clonidine induced significant falls in blood pressure (greater than 20/15 mm Hg) in our normotensive subjects and consistently caused marked sedation and dryness of the mouth. Sedation and salivary flow correlated with plasma clonidine concentration over the range 0 to 4 ng/ml. Falls in blood pressure were related to plasma concentration to 1.5 to 2 ng/ml but at higher concentrations the hypotensive effect was attenuated.