Chronopharmacology of angiotensin II-receptor blockers in XXXX -prone spontaneously @entity101 @entity35 .

@entity917 @entity1 @entity64 @entity101 @entity35 @entity16 @entity15632 @entity2596 @entity11882 @entity3917
Protective effect of @entity917 ( @entity2596 ), an angiotensin II (AII)-receptor blocker ( @entity11882 ), against @entity16 is reported to depend on the dosing time in @entity101 @entity1 . Dosing-time-dependent effect of @entity2596 on survival of @entity64 -prone spontaneously @entity101 @entity35 (SHRSP) under a 12-h lighting cycle was examined. @entity2596 (4 mg/kg per day) and @entity15632 (OM) (1 mg/kg per day), another @entity11882 with a slower dissociation from the AII receptor, were given once daily at 2, 8, 14, or 20 @entity3917 ( @entity3917 ). Dosing-time-dependent differences in plasma drug concentrations and effect on blood pressure (BP) were also evaluated. Survival of SHRSP showed a dosing-time-dependent change during @entity2596 therapy, with a peak at 2 @entity3917 and a trough at 14 @entity3917 . OM equally prolonged survival in all groups. The BP-lowering effect persisted for more than 24 h after dosing of @entity2596 at 2 @entity3917 and of OM at 2 and 14 @entity3917 , but disappeared at 5.5-h after @entity2596 dosing at 14 @entity3917 . Plasma concentrations of @entity2596 and OM were higher after dosing at 2 @entity3917 than at 14 @entity3917 . These results suggest that the chronopharmacological phenomenon of @entity2596 was partly due to the dosing-time-dependent difference in plasma concentration and subsequent duration of the antihypertensive effect. Slower dissociation of OM from AII receptors might have blunted a potential dosing-time-dependent event.
