COMPARISON OF THE PHARMACOKINETICS, PHARMACODYNAMICS, AND SAFETY OF ORAL (CATAPRES) AND TRANSDERMAL (M-5041T) CLONIDINE IN HEALTHY-SUBJECTS

The pharmacokinetic as well as pharmacodynamic properties of a transde rmal clonidine, M-5041T (M) and its safety were compared with those of oral clonidine, Catapres (Nippon Boehringer Ingelheim, Hyogo, Japan). One patch of M containing 6 mg of clonidine was applied on the right chest for 3 days or one tablet of Catapres (.075 mg) was given orally every 12 hours for 3 days in eight healthy subjects. The study was con ducted by a crossover design with 14 to 16 days' interval between the cross-over. Blood and urine samples for clonidine concentration were o btained, and blood pressure (BP) was measured for a 168-hour period af ter application of M and for a 96-hour period after initiation of Cata pres therapy. Plasma concentration of clonidine increased gradually af ter application of M and decreased gradually after removal, whereas th is parameter increased rapidly during the absorption phase and decreas ed rapidly in the elimination phase after each dosage of Catapres. Eli mination half-life of clonidine after removal of M was significantly g reater than that after the final dosage of Catapres. No significant di fference was observed in a maximum plasma concentration or area under the plasma concentration-time curve between the two trials. The BP low ering effects of M and Catapres did not differ significantly. Adverse symptoms occurred more frequently during catapres therapy than during treatment with M. Most of these symptoms were observed when plasma clo nidine concentration was relatively higher in each trial. These result s suggest that M is effective for the treatment of hypertension with a lower incidence of adverse symptoms. Because the current study was no nblind and involved small number of subjects, however, a large control led study is needed to evaluate its safety further.