Pharmacokinetics and tissue distribution of a new partricin A derivative (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diaspartate) in mice.

A single-dose trial in mice (1.25 mg/kg SPA-S-753 or 1 mg/kg amphotericin B [AmB] by intravenous route) was performed to study the pharmacokinetics, tissue distribution, and urinary excretion of a new polyene, SPA-S-753 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diaspartate), in comparison with AmB. Antibiotic concentrations were determined by microbiological assay (agar diffusion method). The elimination half-lives in serum were 15.1 and 19.8 h, respectively, for SPA-S-753 and AmB; the area under the curve from 0 to infinity values were 49.3 for SPA-S-753 and 23.6 microg. h/mL for AmB, because of the higher serum levels of SPA-S-753 found just after administration. The tissue concentrations of SPA-S-753 were lower than those of AmB in liver and lungs but higher in the kidneys. The urine concentrations of SPA-S-753 and the percent of the administered dose recovered from the urine were quite low in mice, whereas those of AmB were higher.