The pharmacokinetics, tissue distribution, and biotransformation of a new class of antitumor agents: mitonafide and pinafide.
The pharmacokinetics, biotransformation, protein binding and tissue distribution of mitonafide and pinafide were studied after single i.v. and oral administration of each drug (20 mg/Kg) in female rats. In pregnant rats a study of cross placental-barrier after i.v. administration of the two drugs was also performed. The drugs were absorbed fairly rapidly with a mean peak plasma level of 7.63 +/- 0.70 micrograms eq/ml for the 3H-mitonafide and with 6.16 +/- 0.77 micrograms eq/ml for the 3H-pinafide between 30 minutes and 1 hour after oral dosing. For both drugs, the pharmacokinetics can be described by a two-compartment open model. The mean elimination half-lives were 17.8 h and 47.5 h for 3H-mitonafide and 3H-pinafide, respectively. Two metabolites for each compound as well as unchanged drugs were identified in urine by TLC and GC/MS by comparison of their chromatographic properties with a number of reference compounds. Approximately 30% of the radioactive drug was excreted over a 48 h period for 3H-mitonafide and 24% for 3H-pinafide in urine, after i.v. administration. The cross placental-barrier studies showed that both 3H-mitonafide and 3H-pinafide were present in the 14-day fetuses.
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007094:Imides; D007546:Isoquinolines / Q000378:metabolism*; D007700:Kinetics; D053644:Naphthalimides; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; C019215:mitonafide; C019222:pinafide