Pharmacokinetics of clonidine in the rat and cat.

To investigate the pharmacokinetic behavior of clonidine, rats were given clonidine intravenously at 125, 250, and 500 micrograms/kg and blood clonidine concentrations were followed for 6 hr. The disposition of clonidine in two brain regions was studied in rats after an i.v. dose of 500 micrograms/kg. The liver clearance in rats was investigated by liver perfusion techniques. The results obtained indicate that the disposition characteristics of clonidine can be described by a two-compartment open model in both rats and cats. The penetration of clonidine into tissues is rapid, and brain levels in rats were about 1.7 times higher than blood levels. Brain tissues were found to be an indistinguisible part of the central (blood) compartment. Dose-dependent pharmacokinetic behavior was found for clonidine in rats at the doses used. This was demonstrated by a decrease of both the rate constant of distribution to the peripheral compartment and the overall elimination rate constant from the body, with increase in dose. As a consequence, the volume of distribution and the clearance both decreased with increasing dose. Possible explanations for the dose-dependent behavior of clonidine are discussed.