Abstract
Flosequinan is a balanced-type vasodilator with a prolonged mode of action due to an approximate 38-hour half-life of its active first metabolite, BTS 53554. As this may lead to tolerance and neurohormonal activation, the acute and long-term pharmacokinetic, hemodynamic, and neurohormonal profile of flosequinan was evaluated. On three consecutive days, 23 patients with heart failure (New York Heart Association classes II-IV), despite digitalis and diuretics, underwent invasive hemodynamic studies after receiving 100 mg oral flosequinan (day 1), placebo (day 2), and 100 mg flosequinan (day 3), followed by repeat invasive evaluation after long-term flosequinan (100 mg daily) for 17 +/- 2 weeks. On each study day, plasma flosequinan levels increased to 1.9 +/- 0.2 mg/L after 1 hour, but returned to baseline levels at 24 hours. In contrast, BTS 53554 increased progressively, reaching relatively high plateau levels (6 mg/L) during chronic therapy. First-dose flosequinan decreased the pulmonary wedge, right atrial pressure, and systemic resistance by 50, 60, and 22%, respectively, whereas the cardiac index was increased by 40%; these effects lasted for 48 hours. During long-term treatment, baseline values of the pulmonary wedge and r...Continue Reading
References
Feb 18, 1992·European Journal of Pharmacology·G Frodsham, R B Jones
Apr 1, 1992·British Journal of Pharmacology·R W GristwoodP Berga
Dec 1, 1992·Journal of the American College of Cardiology·P G CaveroK Chatterjee
Jun 1, 1990·Journal of Cardiovascular Pharmacology·S Greenberg, B Touhey
Oct 1, 1990·Cardiovascular Drugs and Therapy·G A RieggerK Kochsiek
Mar 1, 1991·American Heart Journal·D B Yates
Mar 1, 1991·American Heart Journal·A J Cowley
Aug 1, 1991·The New England Journal of Medicine·UNKNOWN SOLVD InvestigatorsJay N Cohn
Jun 1, 1990·Cardiovascular Drugs and Therapy·G L BartelsH A Kruyssen
Nov 1, 1990·Circulation·K SwedbergL Wilhelmsen
Jul 1, 1988·Journal of Cardiovascular Pharmacology·P D KesslerM Yushak
Sep 1, 1989·Journal of Cardiovascular Pharmacology·R FaloticoA J Tobia
Apr 1, 1989·British Heart Journal·J S ElbornD P Nicholls
Mar 1, 1986·Journal of the American College of Cardiology·M PackerM Yushak
Jun 4, 1987·The New England Journal of Medicine·UNKNOWN CONSENSUS Trial Study Group
Jul 16, 1988·BMJ : British Medical Journal·A J CowleyJ R Hampton
Apr 1, 1987·The American Journal of Cardiology·N SharpeR Luke
Apr 1, 1987·Journal of the American College of Cardiology·A RothU Elkayam
Apr 30, 1986·Clinica Chimica Acta; International Journal of Clinical Chemistry·J J HoffmannT J Benraad
Jan 1, 1987·American Heart Journal·P D Kessler, M Packer
Apr 1, 1983·Circulation·C V LeierD V Unverferth
Sep 27, 1984·The New England Journal of Medicine·J N CohnT Rector
Sep 1, 1982·American Heart Journal·J A FranciosaJ N Cohn
Sep 1, 1981·Circulation·M PackerR Gorlin
Aug 1, 1993·Circulation·B M MassieR M Steingart