Enantioselective pharmacokinetic-pharmacodynamic modelling of carvedilol in a N-nitro-l-arginine methyl ester rat model of secondary hypertension

The Journal of Pharmacy and Pharmacology
Carla Andrea Di VernieroChristian Höcht

Abstract

The role of vascular sympatholytic activity of carvedilol in its antihypertensive effect in N(G)-nitro-l-arginine methyl ester (L-NAME) hypertensive rats was assessed by means of enantioselective pharmacokinetic-pharmacodynamic (PK-PD) modelling. Male Wistar rats were randomly divided into two groups: control rats received tap water to drink for 2 weeks while L-NAME rats received L-NAME solution to drink for 2 weeks. The effects of carvedilol (1 and 5 mg/kg i.v.) on blood pressure, heart rate and blood pressure variability were recorded. Enantioselective carvedilol plasma pharmacokinetics were studied by means of traditional blood sampling. The relationship between carvedilol concentrations and their hypotensive and bradycardic effects was established by means of PK-PD modelling. Vascular sympatholytic activity of carvedilol was assessed by the estimation of drug effects on low frequency blood pressure variability by means of spectral analysis. A dose-dependent increase in volume of distribution, as well as a greater volume of distribution and clearance of S-carvedilol as compared with the R-enantiomer was found in both experimental groups. Although the PK-PD properties of the S-carvedilol chronotropic effect were not altered i...Continue Reading

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Citations

Mar 7, 2014·Expert Opinion on Drug Metabolism & Toxicology·Christian HöchtCarlos Alberto Taira
Feb 1, 2013·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Facundo Martín BerteraChristian Höcht
Oct 18, 2013·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Facundo Martín BerteraChristian Höcht
Sep 1, 2010·Expert Review of Clinical Pharmacology·Christian HöchtCarlos Alberto Taira
Sep 7, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Facundo BerteraChristian Höcht
Nov 4, 2011·Naunyn-Schmiedeberg's Archives of Pharmacology·Facundo Martín BerteraChristian Höcht

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