Disposition and metabolism of the novel macrolide antibiotic CP-163505 in cattle

The plasma pharmacokinetics, lung tissue to plasma concentration ratios, and depletion profiles in edible tissue (liver, muscle, kidney, fat and injection site) for a single subcutaneous dose of a novel macrolide antibiotic, CP-163505 (20-3-dimethylaminopropyl(L-alanyl)amino]-20-deoxo-repromicin), were investigated in crossbred beef cattle. Mean peak plasma concentration of 2.5 ± 0.4 μg/mL, occurring at 0.5 h, was found for CP-163505 following a 5 mg/kg dose ( n  = 5). The pharmacokinetic profile consisted of a distribution phase, followed by an extended terminal elimination phase (t_1/2 of 19 h). The disposition of CP-163505 was characterized by distribution from the plasma into the tissue resulting in lung to plasma ratios of 103 and 87 at 72 h following a single 5 or 10 mg/kg dose, respectively. The depletion of CP-163505 from edible tissues was determined following administration of tritiated CP-163505 at a dose of 10 mg/kg. On day 42, the liver contained the highest mean concentration of total tritium residues, 5.9 ± 3.4 μg/g. CP-163505 was determined to be a significant component of the total residues in liver with 72% on day 3 and 50% on day 42. Three metabolites of CP-163505 were identified by liquid chromatography with mass spectrometry (LC/MS/MS) in liver samples: loss of alanine, formation of an hydroxyl derivative, and sulfate addition to the lactone ring.