Absorption and excretion of miloxacin in mice, rats, and dogs

Abstract

JapanMiloxacin, a synthetic antibacterial agent structurally related to oxolinic acid, has a broad spectrum of activity in vitro against gram-negative bacteria and considerable activity in vivo against infections with these bacteria. These observations led to studies on the absorption and excretion of miloxacin in mice, rats, and dogs after administration of a single oral dose. Studies on oxolinic acid have been included for comparison. Peak serum levels of miloxacin, attained 1 h after administration of 20, 50, and 100 mg/kg to rats and dogs, were approximately 20, 40, and 60 ,Ag/ml, respectively. Peak levels in mice receiving the same dose were 15, 60, and 80 ,ug/ml at 0.5 h. Peak serum levels of oxolinic acid were attained 0.5 to 1 h later than the above times at comparable doses and were one-half to onefourth those of miloxacin. Urinary recovery of miloxacin at the above doses ranged from 3.2 to 6.5% during the 24-h posttreatment period. Recoveries of oxolinic acid were one-half to one-fifth those of miloxacin. At a 50-mg/kg dose, rats excreted 4.6% of the miloxacin in bile in the 20-h posttreatment period.acid, closely related to oxolinic acid (5) in structure, has exhibited a broad spectrum of antibacterial activity in vitro and is especially active against gram-negative bacteria (3). Miloxacin also has significant activity in single-or two-dose regimens against infections with Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, or Serratia marcescens in mice (3). These findings led to studies of the absorption and urinary excretion of this compound after administration of single oral doses to mice, rats, and beagle dogs and the biliary elimination of this compound in rats. Studies on the absorption and urinary excretion of oxolinic acid have been included for comparison. MATERIALS AND METHODSTest compounds. The preparations of miloxacin and oxolinic acid used in the current experiments were synthesized in our laboratory (1, 5). The structures and purities were confirmed by comparison to authentic compounds by infrared, nuclear magnetic resonance, and mass spectra and thin-layer chromatography.Drug administration. Micronized samples of miloxacin and oxolinic acid were suspended in 0.5% aqueous carboxymethylcellulose solution and administered within 1 h of preparation. Mice, rats, and beagle dogs were fasted for 12 to 14 h before administration of single doses of 20, 50, and 100 mg/kg by gavage. The dosed animals were held in metabolism cages suitable for each species; food was withheld for 4 h after administration.Studies in mice. A total of 360 male ICR mice weighing approximately 20 g were used. Fifteen groups, of 10 mice each, were dosed with miloxacin (5 groups for each dose). Animals were decapitated 0.5, 1, 2, 4, and 8 h after dosage. Blood from each group was pooled, kept at room temperature for 0.5 h, and centrifuged at 2,500 rpm to obtain serum, which was immediately frozen and stored at -20°C until assayed. Three groups of 10 mice treated with miloxacin (one group for ea...

Chemotherapeutics

“…Miloxacin, marketed in Japan, has an antimicrobial spectrum and potency similar to that of oxolinic acid. Clinically, it does not seem to have any advantages over oxolinic acid; however, it appears to offer somewhat superior absorption and higher urinary excretion over oxolinic acid [33], [34]. A peak serum concentration of 7.7 mg/mL is achieved in humans 1 -2 h following a 500-mg oral dose [35].…”

Metabolism and disposition of amifloxacin in laboratory animals

“…The remaining 7.7% of the dose appearing in the urine represented radioactive material not associated with any major peak and radioactive material not recovered from the HPLC column. DISCUSSION In rats and rhesus monkeys amifloxacin, like other compounds of the quinoline carboxylic acid class (3,6,7), is well absorbed and rapidly excreted. In both species, 80 to 90% of the dose of amifloxacin is excreted within the first 24 h, with urine being the primary route of elimination.…”

Antibacterial activity of miloxacin

“…These activities of miloxacin were There is a correlation between the in vitro MICs and the 50% effective doses against bacteria used in this studies. Studies concerning levels of miloxacin in serum, bile, and urine are reported in the accompanying paper (3).…”