Pharmacokinetic and pharmacodynamic studies of oral clonidine in normotensive subjects.

The pharmacokinetics of clonidine and its relation to blood pressure response and side effects were studied after single oral doses of 75 micrograms, 150 micrograms and 250 micrograms in normotensive subjects. Following oral administration, the drug was absorbed rapidly after an initial lag time of 19-22 min and peak levels were reached between 2.4 and 2.9 h. Sampling over 48 h was necessary for accurate estimation of pharmacokinetic parameters. Post-peak plasma concentration declined in a monoexponential manner and the half-life of the elimination phase ranged from 9.0 to 15.1 h. Maximum plasma concentration (Cmax) and area under curve (AUC) increased proportionally with increasing doses. Clonidine produced significant reductions in the pulse rate and a dose dependent decrease in blood pressure. Clonidine (150 micrograms) also produced significant reductions in plasma catecholamine levels.