Absorption of clonidine from a halved transdermal system - A pilot study

Objective: To assess whether clonidine bioavailability is compromised when a transdermal system is cut in half. Methods: Seven healthy volunteers were enrolled in this prospective crossover study. In phase I, an intact clonidine 0.1 mg/24 h transdermal system (TS-1) was applied and plasma clonidine concentration was obtained 72 hours after application, after steady-state (48-72 hours) was purported to have been reached. After a minimum seven-day washout period, hall of a clonidine 0.2 mg/24 h transdermal system (1/2 TS-2) was applied in phase II, with plasma clonidine concentrations obtained at 24, 48, 72, 120, and 192 hours following application. Results: Mean plasma clonidine concentrations at 72 hours with TS-1 in phase I were 0.17 ± 0.07 ng/mL. Mean plasma clonidine concentrations at 24, 48, 72, 120, and 192 hours with 1/2 TS-2 in phase II were 0.16 ± 0.11, 0.15 ± 0.06, 0.15 ± 0.05, 0.19 ± 0.4, and 0.20 ± 0.8 ng/mL, respectively. There was no statistically significant difference between mean concentrations at 72 hours in phases I and II, but individual clonidine concentrations between phases varied 50-286%. Individual concentration versus time curves obtained from subjects in phase II lacked a consistent pattern. Conclusions: Although there was no statistically significant difference in mean concentrations at 72 hours, individual clonidine concentration variations may have a clinically significant impact. The lack of a consistent plasma concentration versus time pattern may also be of clinical concern. Based on these results, cutting the clonidine transdermal system may compromise its integrity, and is therefore not recommended.