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Pharmacokinetic characterization of mitonafide in man.

Authors
  • Brode, E
  • Poveda Velasco, A
  • Díaz-Rubio, E
  • Rosell Costa, R
  • Benavides Fissure, A
Type
Published Article
Journal
Methods and findings in experimental and clinical pharmacology
Publication Date
Mar 01, 1992
Volume
14
Issue
2
Pages
131–140
Identifiers
PMID: 1598025
Source
Medline
License
Unknown

Abstract

The pharmacokinetic behavior of mitonafide after intravenous administration (1 h infusions) to patients (118-180 mg/m2) can be described by an open three compartment body model. Mitonafide distributes quasi-instantaneously in a central distribution volume of 102 l/m2 (median) from which it equilibrates with two peripheral compartments of 106 and 258 l/m2, respectively. Its disappearance from plasma is triexponential with half-lives of 0.28, 2.0 and 26.9 h, resulting in a clearance of 69 l/h/m2. This clearance is mainly due to the biotransformation of mitonafide leading among others to amonafide, N-acetyl-amonafide, and N-desmethyl-amonafide, which build up substantial concentrations in plasma. Their quantitative importance in terms of exposures (AUC) relative to the parent compound are 86, 197 and 28%, respectively. Terminal elimination from plasma proceeds with half-lives of 34.3, 17.6 and 27.5 h.

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