Comparative Pharmacokinetics of Three Preparations of the New Antifungal SPK-843

Abstract

The pharmacokinetics and tissue distribution of three preparations of SPK-843 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diascorbate), a new polyene antibiotic with a heptaene structure, were compared in rats after a single 1.25 mg/kg intravenous administration. Blood and tissue samples were obtained at 0.25–96 h after injection. The serum pharmacokinetics of the three dosage forms of the antibiotic, A (5% glucose solution), B (10% lipid emulsion at pH 5.3) and C (10% lipid emulsion at pH 7.5), did not show large differences, the half-lives being 22.2, 26.5 and 23.2 h and the AUC_0–∞ 35.5, 40 and 44.8 µg·h·ml^–1 for preparations A, B and C, respectively. The tissue uptake of the two lipid-based preparations, particularly the spleen uptake, was greater than that of the glucose preparation, suggesting an active role of the lipid vehicle in tissue distribution.