Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves

Authors

D. A. Mzyk, North Carolina State University
R. E. Baynes, North Carolina State University
K. M. Messenger, North Carolina State University
M. Martinez, US Food and Drug Administration
G. W. Smith, North Carolina State UniversityFollow

Date of this Version

2016

Document Type

Article

Citation

Mzyk, D.A., Baynes, R.E., Messenger, K.M., Martinez, M., Smith, G.W. Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves. J. vet. Pharmacol. Therap. 40, 179–191.

Comments

Copyright © 2016 John Wiley & Sons Ltd. Used by permission.

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.