Skin pretreatment and the use of transdermal clonidine

Although therapy with transdermal clonidine is effective in bringing elevated blood pressure under control, this mode of delivery has been associated with localized dermal reactions in a small percentage of patients. Because anecdotal information suggests that a number of physicians have resorted to various dermal pretreatment strategies in an effort to alleviate or eliminate these dermal reactions, we decided to investigate the two most commonly used pretreatment strategies, to determine if they affected the pharmacokinetics and pharmacodynamics of transdermally administered clonidine. Specifically, we examined the effect of dermal pretreatment with 0.5% hydrocortisone cream and with an over-the-counter antacid, magnesium-aluminum hydroxide suspension, on the pharmacokinetics of transdermal clonidine in 10 adult hypertensive males. Patients were randomized to receive one of the two pretreatment regimens or therapy with the patch alone, and after 7 days of treatment and a 14-day washout period, patients were crossed over to receive one of the other therapies. All patients ultimately received all three therapies. We present here the results from the 10 patients enrolled in our study. Our study found a statistical difference detected in maximum plasma concentration (Cmax), steady-state plasma concentration (Css), and apparent clonidine dose delivered (Doseapp) following dermal pretreatment with hydrocortisone compared with the transdermal patch alone. The mean +/- SD relative extents of absorption (Frel) of clonidine following dermal pretreatment with hydrocortisone and magnesium-aluminum hydroxide in respect to the transdermal patch alone were 94.84 +/- 45.69% and 97.65 +/- 59.65%, respectively. No significant difference was detected in this parameter. Supine and sitting blood pressures and pulse rates were similar during treatment with clonidine alone, following dermal pretreatment with hydrocortisone cream, and following pretreatment with magnesium-aluminum hydroxide suspension. In addition, systemic side effects were evenly distributed among treatments. However, dermal side effects were less frequent following pretreatment with hydrocortisone compared with magnesium-aluminum hydroxide and the patch alone. The results of this study suggest that dermal pretreatment with 0.5 percent hydrocortisone cream may significantly alter the plasma concentrations of transdermally administered clonidine without adversely altering the pharmacodynamics.