title: Characterization of the relationship between serum and milk residue disposition of ceftriaxone in lactating ewes.
abstract: 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) mug/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 microg/mL, 1.77 +/- 0.24 h and 67.55 +/- 6.51 microgxh/mL, respectively. For milk the data were: 1.0 h, 8.15 +/- 0.71 mug/mL, 2.2 +/- 0.34 h and 26.6 +/- 5.14 microgxh/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.
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
authors.forename: A
authors.initials: A
authors.lastname: Goudah
authors.forename: H C
authors.initials: HC
authors.lastname: Shin
authors.forename: J H
authors.initials: JH
authors.lastname: Shim
authors.forename: A M
authors.initials: AM
authors.lastname: Abd El-Aty
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002443:Ceftriaxone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D004350:Drug Residues / Q000032:analysis; D005260:Female; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007774:Lactation; D008892:Milk / Q000378:metabolism*; D012756:Sheep / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone