Summary
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 μg eq/ml for the3H-mitonafide and with 6.16±0.77 μg eq/ml for the3H-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 for3H-mitonafide and3H-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 for3H-mitonafide and 24% for3H-pinafide in urine, after i.v. administration.
The cross placental-barrier studies showed that both3H- mitonafide and 3H-pinafide were present in the 14-day fetuses.
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Cid, P.R., Fernandez, E.G., Martin, F.R. et al. The pharmacokinetics, tissue distribution, and biotransformation of a new class of antitumor agents: mitonafide and pinafide. European Journal of Drug Metabolism and Pharmacokinetics 11, 255–267 (1986). https://doi.org/10.1007/BF03189110
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DOI: https://doi.org/10.1007/BF03189110