Vertilmicin Sulfate

The susceptibilities of vertilmicin and seven reference aminoglycosides to modifications by six recombinant aminoglycoside-modifying enzymes, AAC(6′)-Ie, APH(2′′)-Ia, AAC(6′)-Ie-APH(2′′)-Ia, ANT(2′′)-Ia, AAC(6′)-Ib, and AAC(6′)-Ib-cr, were studied by coupled spectrophotometric assays in microtiter plates. In comparison to other aminoglycosides, the susceptibility of vertilmicin was 45.8- to 250.0-fold lower for AAC(6′)-Ie acetylation, 39.2- to 116.7-fold lower for AAC(6′)-Ie-APH(2′′)-Ia acetylation, and 1.8- to 7.5-fold lower for ANT(2′′)-Ia adenylation (except that shown by amikacin) while relatively comparable for AAC(6′)-Ib acetylation, AAC(6′)-Ib-cr acetylation, APH(2′′)-Ia phosphorylation, and AAC(6′)-Ie-APH(2′′)-Ia phosphorylation.

The pharmacokinetics of vertilmicin was investigated in rats and dogs following intramuscular or intravenous administration of vertilmicin. Following a single administration of an intramuscular dose, serum concentrations of vertilmicin peaked at 0.63 h in rats and 0.58 h in dogs. In rats, after intravenous administration of vertilmicin at dosages of 10, 20, and 40 mg/kg, the t1/2 values for vertilmicin were 0.81, 0.76, and 0.86 h, respectively, while after intramuscular administration of vertilmicin at dose of 20 mg/kg, the t1/2 value for vertiImicin was 0.79 h. In dogs, after intravenous or intramuscular administration of vertilmicin at a dose of 10 mg/kg, the t1/2 values for vertilmicin were 0.83 and 0.85 h, respectively. After intravenous dosing to rats vertilmicin was distributed to most organs and tissues, and kidney tissue exhibited the highest exposure, while the tissue with the lowest exposure was the brain. Following single intravenous administration of vertilmicin at a dose of 20 mg/kg to rats, about 81.1% of the vertilmicin was excreted in urine, while only 3.12 and 1.44% of the administered dose was excreted in feces and bile within 48 h. The mean values for the plasma protein binding of vertilmicin were 22.7 and 20.4% in rats and dogs, respectively. These results indicate that vertilmicin was rapidly absorbed and widely distributed into various tissues in rats. The pharmacokinetic behavior of vertilmicin was dose-dependent when increasing doses of vertilmicin were administered intravenously to rats. Renal excretion was the primary elimination route of vertilmicin following intravenous administration to rats.