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Clinical Pharmacokinetics

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01.02.2002 | Original Research Article

Population Pharmacokinetic-Pharmacodynamic Modelling of Angiotensin Receptor Blockade in Healthy Volunteers

verfasst von: Chantal Csajka, Thierry Buclin, Karin Fattinger, Hans R. Brunner, Jérôme Biollaz

Erschienen in: Clinical Pharmacokinetics | Ausgabe 2/2002

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Abstract

Objective

To compare the pharmacokinetic and pharmacodynamic characteristics of angiotensin II receptor antagonists as a therapeutic class.

Design

Population pharmacokinetic-pharmacodynamic modelling study.

Methods

The data of 14 phase I studies with 10 different drugs were analysed. A common population pharmacokinetic model (two compartments, mixed zero- and first-order absorption, two metabolite compartments) was applied to the 2685 drug and 900 metabolite concentration measurements. A standard nonlinear mixed effect modelling approach was used to estimate the drug-specific parameters and their variabilities. Similarly, a pharmacodynamic model was applied to the 7360 effect measurements, i.e. the decrease of peak blood pressure response to intravenous angiotensin challenge recorded by finger photoplethysmography. The concentration of drug and metabolite in an effect compartment was assumed to translate into receptor blockade [maximum effect (E_max) model with first-order link].

Results

A general pharmacokinetic-pharmacodynamic (PK-PD) model for angiotensin antagonism in healthy individuals was successfully built up for the 10 drugs studied. Representatives of this class share different pharmacokinetic and pharmacodynamic profiles. Their effects on blood pressure are dose-dependent, but the time course of the effect varies between the drugs.

Conclusions

The characterisation of PK-PD relationships for these drugs gives the opportunity to optimise therapeutic regimens and to suggest dosage adjustments in specific conditions. Such a model can be used to further refine the use of this class of drugs.

Use of tradenames is for product identification only and does not imply endorsement.

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Titel: Population Pharmacokinetic-Pharmacodynamic Modelling of Angiotensin Receptor Blockade in Healthy Volunteers
verfasst von: Chantal Csajka
Thierry Buclin
Karin Fattinger
Hans R. Brunner
Jérôme Biollaz
Publikationsdatum: 01.02.2002
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 2/2002
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200241020-00005

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Population Pharmacokinetic-Pharmacodynamic Modelling of Angiotensin Receptor Blockade in Healthy Volunteers

Abstract

Objective

Design

Methods

Results

Conclusions

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Objective

Design

Methods

Results

Conclusions

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