Key result
Carvedilol demonstrated increased distribution and enhanced hypotensive activity in fructose-fed hypertensive rats compared with normotensive controls, independent of sympatholytic activity.
Why the study?
Does carvedilol exhibit different pharmacokinetic and pharmacodynamic properties in fructose-induced hypertensive rats compared to normotensive controls?
RCT
randomly assigned
Does carvedilol exhibit different pharmacokinetic and pharmacodynamic properties in fructose-induced hypertensive rats compared to normotensive controls?
Carvedilol demonstrates enantioselective pharmacokinetics with increased distribution and enhanced hypotensive efficacy in a fructose-induced hypertensive rat model.
Answers are grounded in this paper and cite their sources.
Should not alter human prescribing; hypothesis-generating for differential carvedilol effects in hypertensive models.
Cardiovascular effects and pharmacokinetics of carvedilol were assessed in fructose-fed rats using pharmacokinetic-pharmacodynamic (PK-PD) modeling. Male Sprague-Dowley rats were randomly assigned to receive tap water (C rats) or fructose solution (10% w/v) (F rats) during 6 weeks. Effects of carvedilol (1-3 mg/kg i.v.) on blood pressure, heart rate and blood pressure variability were recorded. Carvedilol plasma pharmacokinetics was studied by traditional blood sampling. Relationship between carvedilol concentrations and their hypotensive and bradycardic effects was established by PK-PD modeling. Vascular sympatholytic activity of carvedilol was assessed by estimation of drug effects on low frequency blood pressure variability using spectral analysis. A greater volume of distribution and clearance of S-carvedilol compared to R-enantiomer was found in both experimental groups. Although PK-PD properties of S-carvedilol chronotropic effect were not altered in F rats, hypertensive rats showed greater efficacy to the carvedilol hypotensive response after administration of the higher dose. A similar potency of carvedilol to inhibit sympathetic vascular activity was found in F rats. Carvedilol showed enantioselective pharmacokinetic properties with increased distribution in F rats compared with normotensive animals. An enhanced hypotensive activity of carvedilol was found in F rats compared with C rats, which is not related to enhance sympatholytic activity.
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Bertera et al. (2011) conducted an RCT in fructose-induced hypertension. carvedilol vs. normotensive rats (tap water) was evaluated on hypotensive and bradycardic effects. Carvedilol demonstrated increased distribution and enhanced hypotensive activity in fructose-fed hypertensive rats compared with normotensive controls, independent of sympatholytic activity.
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