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Kinetics of fenoximone, a new cardiotonic, in healthy subjects
Author(s) -
Alken Rudolf G,
Belz Gustav G,
Haegele Klaus D,
Meinicke Thomas,
Schechter Paul J
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.164
Subject(s) - dosing , cmax , pharmacokinetics , chemistry , metabolite , bioavailability , urine , pharmacology , volume of distribution , oral administration , medicine , biochemistry
Fenoximone, a new cardiotonic, was given to six healthy men as a single intravenous dose of 1 mg/kg and a single oral dose of 3 mg/kg as solution in a crossover study. Plasma concentrations were monitored for 8 hr and urine was collected for 24 hr. Peak plasma concentrations (C max ) were reached 30 min after the oral dose. Decay of plasma concentrations was fitted to a mean (±SD) elimination t½ (t½β) of 60 ± 14 min after intravenous injection and 78 ± 26 min after oral dosing. Mean total body clearance for intravenous dosing was 2062 ± 846 ml/min, renal clearance (Cl R ) was 5.3 ± 2.4 ml/min, and extrapolated volume of distribution was 0.37 ± 0.26 l/kg. The sulfoxide derivative was detected as the main metabolite. C max of the sulfoxide metabolite occurred 10 min after the end of the intravenous infusion and 20 to 60 min after oral dosing. From the decay of the plasma concentrations of the sulfoxide, the t½βs were calculated as 132 ± 15 min after intravenous injection and 140 ± 27 min after oral dosing of fenoximone. Cl R of the sulfoxide was 499 ± 106 ml/min after intravenous injection; 24‐hr urinary recovery of the sulfoxide was 75.7% ± 5.7% after intravenous injection and 64.3% ± 10.4% after oral dosing. Mean oral bioavailability of fenoximone was 53% (range 44% to 69%). Clinical Pharmacology and Therapeutics (1984) 36, 209–216; doi: 10.1038/clpt.1984.164