Transdermal Clonidine: a More than Superficial Approach to Hypertension But local skin intolerance might be a problem

Transdermal therapeutic systems (TTSs) involve diffusion of the drug through the intact skin and constitute an efficient means of drug administration. Compared with oral administration, smaller amounts of drug may be necessary in order to achieve the same pharmacological action, while side effects are lessened and patient compliance increased. Already hyoscine [scopolamine] and glyceryl trinitrate [nitroglycerin] are being applied therapeutically by TISs while investigation has shown clonidine, with its low molecular weight and high lipid solubility, also to be a promising candidate for a TIS.

14 men and 7 women with essential hypertension (diastolic BP of more than 95mm Hg) received a placebo TTS for 1 week followed by a clonidine TTS (2.Smg) on their upper arm (replaced each week for 10 weeks). The rate of release was 0.1 mg/24 hours over the 7 days. If the diastolic BP did not fall to 95mm Hg or less in the first 2 weeks the dose was doubled and if necessary after 3 weeks an additional 50mg oral hydrochlorothiazide was given daily.

Overall a fall in blood pressure from 160/106 to 135/89mm Hg was recorded over the 10 weeks, while heart rate remained unchanged. There was a small, but Significant fall in average bodyweight from 76 to 75kg. While 24% of patients achieved normalisation of diastolic BP with only one clonidine-TTS, 33% required 2, and 43% received additional hydrochlorothiazide (3 of these 9 still not falling below 95mm Hg).

Skin reactions, papular in nature, appeared in 6 cases and were associated with erythema and itching. Other adverse effects appeared in 7 cases i.e. dry mouth, constipation, fatigue and sexual disturbances.

While the therapeutic efficacy of this type of treatment was high and its convenience in the long term is self-evident, the proportion of local skin reactions could limit clinical application. Groth. H. et 81 Schwelzef/sche Mmedwnlsche Wochenschf/fl 113. 1841 (Dec 1983) [translated 'rom the of/gmal artIcle published m German)

0156-2703/84/0428-0009/0$01.00/0 © ADIS Press INPHARMA'" 28 Apr 1984 9