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• W1998363105 abstract "The combination therapy of nitrate and selective β-adrenoceptor antagonist has shown benefits for treatment of hypertension and heart disease than either drug alone. The objectives of the present study were to define effects on the antihypertension activity and pharmacokinetics of a novel transdermal patch incorporating isosorbide dinitrate (ISDN) with bisoprolol (BP). The 3:2 ratio of ISDN to BP (mg/mg) in the transdermal patches exhibited better anti-hypertension effect synergistically with a similar inhibiting heart rates effect to that of BP alone in renovascular hypertensive rats, and was therefore selected as a final formulation. The in vitro transdermal penetration of both ISDN and BP from the patches displayed a zero-order process, and the penetration rate constants were 7.4 μg/(cm2 h) for ISDN, and 5.9 μg/(cm2 h) for BP, respectively. After transdermal administration at single dose or multiple doses, the synergistic anti-hypertension effect was confirmed in spontaneously hypertensive rats also. The effect of each patch lasts for 3 days, and increased with the total dose of two drugs (2 mg/cm2, ISDN:BP = 3:2, mg/mg), showing a dose dependant manner. After transdermal administration to rabbits, the absolute bioavailabilities were 33.6% for ISDN, and 31.3% for BP, respectively. The maximal concentrations (Cmax) of both drugs were significantly reduced while the areas under the plasma concentration–time curve (AUC), and mean residence times (MRT) were evidently increased and extended, respectively. As a patient-friendly, convenient, and multi-day dosing therapeutic system, the transdermal patches incorporating ISDN and BP could be promising for prevention and treatment of hypertension." @default.
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• W1998363105 date "2007-06-01" @default.
• W1998363105 modified "2023-10-17" @default.
• W1998363105 title "A novel transdermal patch incorporating isosorbide dinitrate with bisoprolol: In vitro and in vivo characterization" @default.
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• W1998363105 doi "https://doi.org/10.1016/j.ijpharm.2006.12.030" @default.
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