Pharmacokinetics of transdermally delivered clonidine

We detail a series of pharmacokinetic investigations to determine the dose linearity, the effect of site of application, the duration of steady-state plasma concentrations, and the effect of chronic application when clonidine is administered transdermally. Dose linearity was assessed in six subjects with normotension after application of increasing sizes of transdermal clonidine systems (3.5, 7.0, and 10.5 cm2 size) to the upper outer arm. Of the six subjects studied, five had linear relationships between clonidine plasma concentrations at steady state and system size of greater than 0.975; in the sixth subject the correlation was greater than 0.90. The mean steady-state plasma concentrations with 3.5, 7.0, and 10.5 cm2 systems were 0.39, 0.84, and 1.12 ng/ml, respectively. The influence of site and duration of application on the absorption of transdermal clonidine was studied in eight subjects with normotension by use of the 3.5 cm2 system. The mean steady-state plasma concentration over the time interval from 3 to 7 days after application to the arm or to the chest did not significantly differ. When a system was left on the chest or arm for a total of 11 days (4 days beyond the recommended time to change systems), the plasma concentrations of seven of eight subjects with application to the arm and of six of eight subjects with application to the chest remained constant through day 11. The influence of consecutive applications of 3.5 cm2 transdermal clonidine systems on steady-state plasma clonidine concentrations was also studied in eight subjects with normotension over an 11-day period.(ABSTRACT TRUNCATED AT 250 WORDS)