| The pharmacokinetic parameters of doxycycline, a structural isomer of tetracycline, were determined after a single intravenous administration to calves with and without mature rumen function, piglets, adult mongrel dogs and adult mixed breed cats. For that purpose, a sensitive and selective high-performance chromatographic assay was developed to quantitate doxycycline concentrations in tissues and body fluids. Doxycycline disposition was best described by means of an open 2-compartment model in all species studied. Doxycycline elimination half-life was longest in calves with mature rumen function (median 14.17 hours) and shortest in cats (median 4.56 hours). In piglets, secondary peaks in the log serum concentration-time profile suggested discontinuous enterohepatic cycling.; Photodiode array detection of high-performance liquid chromatographic effluent and mass spectrometric analysis of serum and urine did not detect metabolites of doxycycline in any of the species studied. An absence of biotransformation of doxycycline is thus suggested. Radiolabelled studies would be definite.; Doxycycline was more than 90% bound to serum proteins. The extent of binding was comparatively highest in cats (98.35%) and thereby influenced values of the volume of distribution and total body clearance. The affinity of doxycycline for crystalline plasma albumin fraction V, originating from sheep, dogs, cats, cows, pigs and men, was evaluated by means of double reciprocal and Scatchard plots. Mathematical modeling and weighted least-squares nonlinear regression analysis of each Scatchard plot identified one binding component characterized by one high affinity binding site, and a second component attributed to nonspecific binding to albumin. Association constants for this binding site ranged from 38,471 {dollar}pm{dollar} 13,369 (SEM) liters/mole for the interaction of doxycycline with ovine albumin to 6,405 {dollar}pm{dollar} 2,375 liters/mole for the interaction of doxycycline with human albumin.; In horses, intravenous administration of doxycycline produced collapse, cardiac arrhythmias, and death, presumably secondary to ventricular fibrillation. Slow infusions of 1 mg/kg body weight over a period of 15 minutes induced ventricular tachycardia and increased blood pressure in all horses studied. This severe reaction precluded conducting pharmacokinetic studies in this species.; It is concluded that doxycycline may be a valuable antimicrobial drug for use in food animals and companion animal species, pending the development and testing of practicable formulations. The intravenous use of doxycycline in horses should be discouraged. |
