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Pharmacodynamic models for the cardiovascular effects of moxonidine in patients with congestive heart failure.
- Source :
-
British journal of clinical pharmacology [Br J Clin Pharmacol] 2001 Jan; Vol. 51 (1), pp. 35-43. - Publication Year :
- 2001
-
Abstract
- Aims: To assess the pharmacodynamics of moxonidine in patients with functional NYHA Class II-III congestive heart failure (CHF).<br />Methods: A parallel population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed to assess the effect of moxonidine (0.1, 0.2, 0.3 mg twice daily) and placebo treatment on plasma noradrenaline (NA) levels, standing systolic blood pressure (SBP), and heart rate (HR) over 12 weeks in 97 patients with CHF using a parallel group design with dose escalation. A sequential analysis was also developed, where the relative changes in NA concentration were related to both SBP and HR.<br />Results: In the parallel PD analysis, an effect delay was shown for all three end points (NA, SBP, and HR). An inhibitory Emax model was used to characterize the concentration-effect relationships. For SBP and HR, the EC50 value increased over time. For NA, there was a positive baseline drift over the 12 weeks; this was interpreted as disease progression. Moxonidine delayed this increase by 9.8 weeks. For SBP, there was a circadian pattern at baseline. In the sequential PD analysis, the relationship between the drug response (NA) and SBP or HR was best described by an inhibitory Emax model. No effect delays between the response and effects were found.<br />Conclusions: Effects of moxonidine on NA, SBP, and HR could be quantified by an effect compartment model in the presence of disease progression and circadian variations. Disease progression, as judged by increasing NA levels with time, was delayed by moxonidine. A direct relationship was found between NA and SBP/HR.
- Subjects :
- Adult
Aged
Algorithms
Anti-Arrhythmia Agents pharmacokinetics
Anti-Arrhythmia Agents therapeutic use
Blood Pressure drug effects
Female
Heart Failure blood
Heart Failure physiopathology
Heart Rate drug effects
Humans
Imidazoles pharmacokinetics
Imidazoles therapeutic use
Male
Middle Aged
Models, Biological
Norepinephrine blood
Anti-Arrhythmia Agents pharmacology
Heart Failure drug therapy
Imidazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0306-5251
- Volume :
- 51
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- British journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11167663
- Full Text :
- https://doi.org/10.1046/j.1365-2125.2001.01320.x