title: Disposition and metabolism of the novel macrolide antibiotic CP-163505 in cattle.
abstract: 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 micrograms/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 (t1/2 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 micrograms/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.
authors.affiliation: Animal Health Product Development, Safety and Metabolism, Pfizer Central Research, Groton, CT 06340, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Linhares
authors.forename: L P
authors.initials: LP
authors.lastname: Harran
authors.forename: T J
authors.initials: TJ
authors.lastname: Strelevitz
authors.forename: J W
authors.initials: JW
authors.lastname: Gauthier
authors.forename: M J
authors.initials: MJ
authors.lastname: Cole
authors.forename: R L
authors.initials: RL
authors.lastname: Hassfurther
authors.forename: J E
authors.initials: JE
authors.lastname: Risk
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002417:Cattle; D002853:Chromatography, Liquid; D004350:Drug Residues / Q000032:analysis*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D018942:Macrolides; D013058:Mass Spectrometry; D009132:Muscles / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D000900:Anti-Bacterial Agents; C111763:CP 163505; D018942:Macrolides