Metabolic studies of pactamycin

Pactamycin levels in serum or urine could be determined either by a tissue culture assay or the disc-plate assay using Bacillus subtilis. After intravenous administration, the antibiotic level in the sera of various animal species decreased rapidly, with complete disappearance of the activity within 30 min. This decrease was not attributable to inactivation by blood or irreversible binding by tissues. Excretion in urine accounted for less than 1 per cent of the total antibiotic injected. In vitro, pactamycin was degraded by liver slices of dog at the rate of 487 μg/hr per g liver slice. If the counterpart of the in vitro-system operates in vitro, then the rapid inactivation of pactamycin and low recoveries in vitro can be explained. Cancer patients treated with the drug also showed low blood levels and poor recovery from urine; however, patients suffering from extensive liver metastasis had higher blood levels and excreted more pactamycin than those with no liver involvement. This could be attributed to the inability of the metastatically involved liver to degrade the antibiotic and could account for the somewhat more violent reactions of these patients to the drug.