Pharmacokinetics of a New Derivative of Partricin A (SPA-S-753) in Rodents

Pharmacokinetics of a new semisynthetic polyene antibiotic (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide) in the form of its diaspartate salt (code SPA-S-753) was studied in rats and mice following intravenous injection and in rats following oral administration at different dose levels. In rats the urinary and biliary recovery after intravenous administration was also determined. Rats and mice received a single intravenous injection of 1.25 and 2.5 mg/kg of SPA-S-753 (about 1–2 mg/kg of free base) or 1 mg/kg of amphotericin B as reference drug. Blood samples were obtained at 5 min to 96 h after injection. The half-lives at the elimination phase in serum were 21.3, 26.5, 10.8 h in rats and 11.7, 13.7, 19.8 h in mice, respectively, for 1.25 and 2.5 mg/kg of SPA-S-753 and 1 mg/kg of amphotericin B. The values of AUC 0–∞ for SPA-S-753 were about 5 times higher in rats and twice higher in mice than those for amphotericin B. Rats received also a single oral dose of 200 or 500 mg/kg of SPA-S-753. Serum samples were obtained at 0.5–96 h after dosing. The compound is poorly absorbed by the oral route. The mean cumulative urinary recovery of SPA-S-753 at 48 h after intravenous injection of 1.25 mg/kg in rats accounts only for 0.5% of the dose, while the cumulative recovery from the bile at 10 h after 2.5 mg/kg i.v. administration in rats accounts for 5.5% of the dose.