Pharmacokinetics and side-effects of clonidine.

A single oral dose of clonidine 300 microgram was administered to 8 healthy, normotensive subjects and the time course of its plasma concentrations was followed for 24 h. The plasma concentration of clonidine rose to a peak of 1.17 +/- 0.12 ng/ml at about 2 h: the absorption half-life was 0.6 +/- 0.2 h. Elimination followed first order kinetics with a half-life of 7.7 +/- 2.0 h. The correlation between the two most common side-effects of clonidine, sedation and dryness of the mouth, with the time course of its plasma concentrations was highly significant, p less than 0.01. All the subjects complained of severe sedation. During continuous administration of clonidine (75 microgram t.i.d.) for one week a steady state serum level of 0.30-0.35 ng/ml was achieved. One 75 microgram tablet of clonidine raised the serum level to about 0.69 +/- 0.13 ng/ml in two hours. After cessation of dosing, the serum level declined with a half-life of 7.5 +/- 1.5 h. The urinary excretion of unchanged clonidine was found to be about one third of the administered dose in 24 h during continuous administration and in the first 24 h after the single oral dose.