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.
Rimaroli
Claudio
C
Research Laboratories, Società Prodotti Antibiotici SpA, Via Biella 8, 20143 Milan, Italy. rimaroli@spaspa.it
Bonabello
Angelo
A
Sala
Patrizio
P
Bruzzese
Tiberio
T
D000666:Amphotericin B / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D011090:Polyenes / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution
D000935:Antifungal Agents; D011090:Polyenes; C106480:SPA-S-753; D000666:Amphotericin B