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Disposition and metabolism of the novel macrolide antibiotic CP‐163505 in cattle
Author(s) -
Linhares M.C.,
Harran L.F.,
Strelevitz T.J.,
Gauthier J.W.,
Cole M.J.,
Hassfurther R.L.,
Risk J.E.
Publication year - 1998
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1046/j.1365-2885.1998.00125.x
Subject(s) - pharmacokinetics , chemistry , chromatography , metabolism , antibiotics , metabolite , high performance liquid chromatography , urine , pharmacology , biochemistry , biology
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.