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  • Title: Antihypertensive effects of a new transdermal delivery system for clonidine (M-5041T) in spontaneously hypertensive rats.
    Author: Ishii R, Naruse T, Tagawa T, Yamahata T, Dote S, Hamada K, Ishida T, Funabiki K, Namba K.
    Journal: Arch Int Pharmacodyn Ther; 1994; 327(3):294-308. PubMed ID: 7848013.
    Abstract:
    The antihypertensive effects of a new transdermal delivery system for clonidine (clonidine tape; M-5041T) were investigated in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. In spontaneously hypertensive rats, M-5041T, at doses of 0.5-4.5 mg/kg (1.25-11.25 cm2/kg), produced a dose-dependent decrease of both systolic blood pressure and heart rate for 24 hr during transdermal application. These significant hypotensive effects lasted for 24 hr following the patching of M-5041T on the back of the animals at a dose of 4.5 mg/kg. In normotensive Wistar-Kyoto rats, the hypotensive and bradycardic effects of M-5041T were weak compared with those in spontaneously hypertensive rats. In both rat strains, M-5041T (4.5 mg/kg) caused behavioral changes such as sedation, piloerection and exophthalmos, accompanied by hypotensive effects. Both M-5041T (1.5 mg/kg) and clonidine (50 micrograms/kg, subcutaneously and 100 micrograms/kg, orally) induced similar hypotensive effects, accompanied by sedation. The hypotensive effects following transdermal M-5041T or systemic clonidine administrations were correlated with the time courses of the plasma clonidine concentration. In contrast to clonidine administered subcutaneously or orally, M-5041T produced a gradual increase in the plasma clonidine concentration, which persisted at a consistent level for at least 12 hr thereafter. Significant hypotensive effects lasted for 12 and 24 hr following M-5041T patching at 1.5 and 4.5 mg/kg, respectively. The present findings suggest that M-5041T can serve as an efficient and useful antihypertensive transdermal delivery system to achieve persistent blood pressure control.
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