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Invasive Pharmacodynamics of Fosinopril in Patients with Congestive Heart Failure
Author(s) -
Ford Neville F.,
Natarajan Chandra,
Fulmor I. Edgar,
Smith R. A.,
Hui Ka Kit
Publication year - 1995
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1995.tb04121.x
Subject(s) - pharmacodynamics , heart failure , fosinopril , medicine , cardiology , pharmacokinetics , blood pressure , angiotensin converting enzyme
Five patients with NYHA Class III CHF received 5 mg of fosinopril on each of 4 days. Hemodynamics were measured with a Swan‐Ganz catheter after dosing on day 1. Measurements of plasma fosinoprilat, ACE activity, renin, and aldosterone were obtained. An E max model was used to fit the effect‐site concentration and mean arterial pressure change. A linear model was used to fit the effect‐site concentration and the pulmonary artery wedge pressure (PAWP) change. At steady state on day 4, AUC 0–24 was 1668 ± 476 ng.hr/mL and C max was 143.5 ± 33.6 ng/mL. The mean elimination half‐life of fosinoprilat was 11.3 ± 0.7 hours, and median T max occurred at 3 hours, corresponding to maximum plasma ACE inhibition. Plasma renin activity was unchanged, and mean plasma aldosterone level declined. E max modeling using fosinoprilat concentrations and mean arterial pressure showed good prediction of the pharmacodynamic effects from the effect‐site concentration. A linear relationship was observed between the effect‐site concentrations of fosinoprilat and PAWP. When expressed in an E max model, the pharmacodynamic actions of fosinopril in patients with CHF are a reflection of its pharmacokinetics.