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HAEMODYNAMIC EFFECTS OF A SINGLE LOW DOSE OF PRAZOSIN IN PATIENTS WITH CHRONIC CONGESTIVE CARDIAC FAILURE CORRELATIONS WITH PHARMACOKINETICS
Author(s) -
Horowitz J. D.,
Dy M. K.,
Jarrott B.,
Brennan J. B.,
Oliver L. E.,
Goble A. J.,
Louis W. J.
Publication year - 1984
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1984.tb00234.x
Subject(s) - prazosin , pulmonary wedge pressure , pharmacokinetics , hemodynamics , heart failure , vascular resistance , cardiac output , medicine , cardiac index , blood pressure , cardiology , heart rate , anesthesia , antagonist , receptor
SUMMARY 1. The haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m.=4.5 to 19.4, s.e.m.=5.1 mmHg; P <0.001), mean arterial blood pressure (from 94.5, s.e.m.=6.0 to 85.4, s.e.m.=5.0 mmHg; P <0.01), and systemic vascular resistance (from 1690, s.e.m.=360 to 1420, s.e.m.=200 dyn. s/cm 5 ; P <0.05) and a rise in cardiac index from 1.98 (s.e.m.=0.07) to 2.28 (s.e.m.=0.16) litres/min per m 2 ( P <0.05). There was a non‐significant fall in heart rate. 2. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m.=1.4) ng/ml, occurring 2.1 (s.e.m.=0.4) h after drug ingestion. The mean elimination half‐life was 5.1 (s.e.m.=0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half‐life and area under the concentration‐time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters. 3. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral doses of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initial doses.