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• W1567446168 abstract "To investigate whether (i) angiotensin receptor occupying profiles of angiotensin II receptor blockers (ARBs) vary among the drugs and (ii) such differences contribute to the degree of their pleiotropic effects.In a randomized, three phase crossover study, nine hypertensive patients received repeated doses (each recommended starting dose for 7 days and then each maximum recommended dose for 20 days) of irbesartan, valsartan and candesartan. The time course profiles and trough level of receptor occupancy were determined on days 7 and 28, respectively. The pleiotropic effect related parameters were measured on days 0 and 28 in each trial.Of the pleiotropic effect related parameters investigated, urinary 8-isoprostane, fasting serum insulin and homeostasis model assessment of insulin resistance index were more suppressed after 4 weeks treatment with irbesartan than after candesartan and valsartan therapy, respectively. The maximum, area under the curve and trough values of receptor occupancy significantly differed between the ARBs [geometric mean (and 95% CI) of trough value 18.1 (12.9, 25.3) for irbesartan, 9.6 (6.0, 15.3) for valsartan and 5.5 (2.8, 10.8) for candesartan, respectively] and were negatively correlated with the change in urinary 8-isoprostane (r = -0.46 - -0.55, P < 0.05), but not the markers of insulin resistance (r = 0.02-0.15, P = 0.46-0.94).Our results demonstrate that the receptor occupying profiles are different among the ARBs. This class of drugs might have both receptor occupancy dependent and independent pleiotropic effects." @default.
• W1567446168 created "2016-06-24" @default.
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• W1567446168 date "2013-01-10" @default.
• W1567446168 modified "2023-09-23" @default.
• W1567446168 title "Relationship between the receptor occupancy profile and pleiotropic effects of angiotensin II receptor blockers" @default.
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• W1567446168 doi "https://doi.org/10.1111/j.1365-2125.2012.04358.x" @default.
• W1567446168 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3579256" @default.
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