The subcellular distribution of 14C-lidamidine and its metabolites.
Examination of the subcellular distribution of 14C-lidamidine and its metabolites in rat liver showed that the majority of radioactivity appeared in the postmicrosomal supernatant fraction, with lysosomes and microsomes having the highest relative specific activity (RSA) of the particulate fractions. When the subcellular distribution pattern was corrected for cross-contamination, based on the distribution of subcellular fraction marker enzymes, there was a significant decrease in the lysosomal RSA with an attendant increase in the microsomal RSA. Thin-layer chromatography of subcellular fraction extracts revealed different distribution patterns for lidamidine and metabolites in each fraction. The whole homogenate and cytosol fraction contained mostly polar metabolites (76-91%), whereas the particulate fractions contained 37-50% of their radioactivity as polar metabolites. The highest percentages of unchanged lidamidine and its more pharmacologically active, demethylated metabolite were associated with the mitochondrial and microsomal fractions.
D000818:Animals; D001711:Biotransformation; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010671:Phenylurea Compounds / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D010671:Phenylurea Compounds; C020918:lidamidine