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.
Bruzzese
T
T
Research Laboratories, Società Prodotti Antibiotici SpA, Via Biella 8, I-20143 Milan, Italy. researches@spaspa.it
Galmozzi
M R
MR
Ferrari
V M
VM
Sala
P
P
Bonabello
A
A
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D011090:Polyenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000935:Antifungal Agents; D011090:Polyenes; C115650:SPA S 843