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.
ASJC Scopus subject areas
- Pharmaceutical Science