Pharmacokinetics of tilmicosin in beef cattle following intravenous and subcutaneous administration.

The intravenous pharmacokinetic profile of tilmicosin is yet to be achieved because of the cardiovascular effects of tilmicosin. This study summarizes two pharmacokinetic studies that provided complete pharmacokinetic profile of tilmicosin in cattle. The first study was a pharmacokinetic study of tilmicosin in beef calves dosed by i.v. infusion over 5 h. The second study was a subcutaneous (s.c.) pharmacokinetic study comparing the pharmacokinetic profile of tilmicosin in light (approximately 170 kg) and heavy (approximately 335 kg) beef cattle and comparing the labeled dose range of 10 or 20 mg/kg dose. The data from the two different studies were used to calculate bioavailability values, which support the assumption that tilmicosin is 100% bioavailable in cattle. The results from the second study showed that the weight of an animal when administered tilmicosin does not have a significant effect on exposure, but did demonstrate that doubling the dose of tilmicosin administered doubles the systemic exposure to tilmicosin.

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 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.

Isolation and characterization of an interleukin-8-like peptide in the bovine species.

Human interleukin-8 (IL-8) is a biologically active peptide which displays chemo-attractive activity for neutrophils and T-cells. The molecule is produced by a variety of cell types upon exposure to lipopolysaccharide, interleukin-1 and tumor necrosis factor. Recombinant human IL-8 also stimulates chemotaxis of bovine cells in a dose dependent manner. The purpose of this series of studies was to investigate the ability of bovine cells to produce an active IL-8-like molecule and to determine if bovine cells respond to human recombinant IL-8. Stimulation of purified peripheral blood mononuclear cells results in the time dependent production of an IL-8-like molecule as determined using an anti-human IL-8 ELISA assay and a bovine neutrophil chemotactic assay. Physical characterization indicates that the biological activity of the molecule was significantly reduced by heat inactivation at 56 degrees C for 30 min or exposure to extreme acidic or basic conditions. The peptide was affinity purified using an anti-human IL-8 antibody produced from ATCC hybridoma HB9647. SDS-PAGE analysis yields a distinct band at 7.8 kDa. The isoelectric point of the purified protein was determined to be 8.65. Biological activity of the purified protein was confirmed and the anti-human IL-8 antibody was capable of partially neutralizing the chemotactic activity.