Pharmacokinetic characterization of mitonafide in man.
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.
Brode
E
E
Knoll AG, Ludwigshafen, Germany.
Poveda Velasco
A
A
Díaz-Rubio
E
E
Rosell Costa
R
R
Benavides Fissure
A
A
D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D005260:Female; D006207:Half-Life; D006801:Humans; D007094:Imides; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D053644:Naphthalimides
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; C019215:mitonafide