title: Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves.
abstract: The objective of this study was to compare active drug concentrations in the plasma vs. different effector compartments including interstitial fluid (ISF) and pulmonary epithelial lining fluid (PELF) of healthy preruminating (3-week-old) and ruminating (6-month-old) calves. Eight calves in each age group were given a single subcutaneous (s.c.) dose (8 mg/kg) of danofloxacin. Plasma, ISF, and bronchoalveolar lavage (BAL) fluid were collected over 96 h and analyzed by high-pressure liquid chromatography. PELF concentrations were calculated by a urea dilution assay of the BAL fluids. Plasma protein binding was measured using a microcentrifugation system. For most preruminant and ruminant calves, the concentration-time profile of the central compartment was best described by a two-compartment open body model. For some calves, a third compartment was also observed. The time to maximum concentration in the plasma was longer in preruminating calves (3.1 h) vs. ruminating calves (1.4 h). Clearance (CL/F) was 385.15 and 535.11 mL/h/kg in preruminant and ruminant calves, respectively. Ruminant calves maintained higher ISF/plasma concentration ratios throughout the study period compared to that observed in preruminant calves. Potential reasons for age-related differences in plasma concentration-time profiles and partitioning of the drug to lungs and ISF as a function of age are explored.
authors.affiliation: Department of Population Health and Pathobiology and the Food Animal Residue Avoidance, Depletion Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Mzyk
authors.affiliation: Department of Population Health and Pathobiology and the Food Animal Residue Avoidance, Depletion Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Baynes
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: K M
authors.identifier: http://orcid.org/0000-0001-8161-4482
authors.initials: KM
authors.lastname: Messenger
authors.affiliation: US Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Rockville, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Martinez
authors.affiliation: Department of Population Health and Pathobiology and the Food Animal Residue Avoidance, Depletion Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Smith
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001826:Body Fluids / Q000737:chemistry*; D002417:Cattle / Q000502:physiology*; D004063:Digestion / Q000502:physiology*; D024841:Fluoroquinolones / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C068581:danofloxacin