Overview of SPA-S-843 in vitro Activity against Filamentous Fungi

Single- and multiple-administration trials in rats were performed in this study to assess the serum and tissue concentrations of SPK-843 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diascorbate), a new polyene antibiotic with a heptaene structure. A dose of 1.25 mg/kg (roughly 1 mg/kg of free base) by intravenous route was used both for the single- and multiple-administration trials. The single-administration trial was carried out in comparison with amphotericin B (AmB) at intravenous doses of 1 mg/kg. Plasma samples were drawn at intervals from 15 min to 96 h after injection. The elimination half-lives were 22.15 and 18.15 h, and the area under the curve to infinity (AUC_0–∞) values were 35.52 and 10.33 µg·h·ml^–1, respectively, for SPK-843 and AmB. Both drugs showed an extensive tissue distribution, with higher uptake by the kidneys, followed by the liver, spleen and lungs for SPK-843, and higher uptake by the spleen, followed by the lungs, liver and kidneys for AmB. The multiple-administration trial (1.25 mg/kg/day for 7 days) led to sustained serum and tissue concentrations. On the seventh day, the rats were bled at intervals from 5 min to 96 h after dosing. The serum elimination half-life and AUC_0–∞ values were roughly twice those of the single-dose study (41.4 h and 72.1 µg·h·ml^–1, respectively). Also, the half-lifes and AUCs from 0 to ∞ of tissues were greater than those in the single-dose trial.

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics in Rats of N-Dimethylaminoacetyl-Partricin A 2-Dimethylaminoethylamide Diascorbate (SPK-843)

Bruzzese¹,

Galmozzi²,

Buffa³

et al. 2001

“…In an in vitro study against 116 strains of Candida, Cryptococcus and Saccharomyces spp., SPK-843 showed better inhibitory activity against all yeasts examined and better fungicidal activity against Candida albicans, Candida glabrata, Candida krusei and Candida tropicalis than did amphotericin B, which at present is the first choice for the treatment of severe systemic mycoses [6][7][8]. Other in vitro studies also underline its strong antifungal activity against yeast-like and filamentous mycetes [9,10].…”

Section: Introductionmentioning

confidence: 99%

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

Bruzzese¹,

Galmozzi²,

Ferrari³

et al. 2001

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.

“…More recently the studies have been continued on two hydrosoluble salts of the above compound, namely the diaspartate salt SPA-S-753 [2] and the diascorbate salt SPA-S-843 [3,4] and both, while showing some limited difference in their chemical and physical properties, confirmed their excellent biological properties. SPA-S-753 proved more effective in vitro than amphotericin B (AmB) against several strains of yeast-like (Candida, Cryptococcus, Trichosporon) and filamentous (Aspergillus) mycetes [2,[5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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

Galmozzi¹,

Bruzzese²,

Buffa³

et al. 2000

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.