Comparative pharmacokinetics of three preparations of the new antifungal SPK-843.

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-infinity) 35.5, 40 and 44.8 microg.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. Copyright 2001 S. Karger AG, Basel