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Characterization of the relationship between serum and milk residue disposition of ceftriaxone in lactating ewes
Author(s) -
GOUDAH A.,
SHIN H. C.,
SHIM J. H.,
ABD ELATY A. M.
Publication year - 2006
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 - 10.1111/j.1365-2885.2006.00749.x
Subject(s) - urine , ceftriaxone , pharmacokinetics , volume of distribution , chemistry , elimination rate constant , oral administration , crossover study , chromatography , pharmacology , zoology , antibiotics , medicine , biology , biochemistry , placebo , alternative medicine , pathology
The present study was planned to investigate the serum disposition kinetics and the pattern of ceftriaxone elimination in milk and urine of lactating ewes ( n = 6) following i.v. and i.m. administration. A crossover study was carried out in two phases separated by 15 days. Ceftriaxone was administered at a dosage of 10 mg/kg b.w. in all animals. Serum, milk and urine samples were collected between 0 and 72 h and a modified agar diffusion bioassay method was used to determine the percentage of protein binding and to measure serum, urine and milk concentrations of ceftriaxone. The drug was detected between 5 min and 48 h postdosing. Concentrations of 0.56 (10 h) and 0.52 (12 h), 0.22 (10 h) and 0.19 (12 h), and 2.18 (24 h) and 2.11 (48 h) μ g/mL were measured in serum, milk and urine following i.v. and i.m. administration, respectively. Individual pharmacokinetic parameters were determined by fitting a two‐compartment model to the serum and one‐compartment open model to the milk concentration–time profiles. After i.v. dosing, the elimination rate constant and elimination half‐life were 0.4 ± 0.05/h and 1.75 ± 0.02 h, respectively. The volume of distribution at steady state (V dss ) of 0.28 ± 0.15 L/kg reflected limited extracellular distribution of the drug with total body clearance ( Cl tot ) of 0.14 ± 0.10 L/h/kg. Following i.m. administration, the mean T max obs , C max obs , t 1/2el and AUC values for serum data were: 0.75 h, 23.16 ± 2.94 μ g/mL, 1.77 ± 0.24 h and 67.55 ± 6.51 μ g·h/mL, respectively. For milk the data were: 1.0 h, 8.15 ± 0.71 μ g/mL, 2.2 ± 0.34 h and 26.6 ± 5.14 μ g·h/mL, respectively. The i.m. bioavailability was 83.6% and the binding percentage of ceftriaxone to serum protein was 33%. Concentrations of ceftriaxone in milk produced by clinically normal mammary glands of ewes were consistently lower than in serum; the kinetic value AUC milk / AUC serum and C max milk / C max serum ratios was<0.4. These low values indicated poor distribution and penetration of ceftriaxone from the bloodstream to the mammary gland of lactating ewes following both routes.