Pharmacology – Absorption
After oral application, Baytril® is readily absorbed from the duodenum and jejunum (13) and reaches high plasma concentrations within a short time. Resorption from parenteral injection sites is nearly complete (13). In general, bioavailability is excellent with similar plasma concentration curves after both oral and parenteral application.
Once-daily administration of the total dose has therapeutic advantages over splitting the dose into two portions. Single administration also increases convenience for the animal owner.
Activity with Pus
Baytril® readily penetrates cellular debris, pus, and inflammatory secretions and maintains its activity even against pathogens covered by a layer of inflammatory products.
In an environment where the degradative products of inflammation such as cellular debris or purulent exudate present an acidic, hyperosmolar, and hypoxic environment, the activity of conventional antibiotics may be lowered or even totally impaired. The amphoteric and zwitterionic properties of the molecule make Baytril® highly lipid soluble.
Due to its lipophilic nature, Baytril® is able to cross cell membranes (7) and thus attain high extracellular and intracellular concentrations.
Bacteria invade tissues and liberate toxins and other substances.
Granulocytes are attracted to the affected area and migrate from the dilated vascular bed in great numbers.
Mast cells degranulate and liberate vasoactive amines.
The action of prostaglandins and leukotrienes allow leakage of plasma and protein.
Neutrophils and macrophages phagocytize bacteria, but also excrete numerous proteolytic enzymes, chemotactic, and chemokinetic substances that attract more white cells.
Vasodilation is increased and the cardinal signs of inflammation appear.
The intercellular matrix is damaged; fibroblasts start forming collagen and proteoglycans.
In contrast to some antibiotics of other classes, it is not sequestered inside the cell and bound to subcellular organelles, but remains free in cytosol as an active compound (7). Thus, obligate or facultative intracellular pathogens such as mycoplasmas, chlamydiae, Rickettsiales, or staphylococci are eliminated as well.
Accumulation in Phagocytic Cells
Bacteria such as staphylococci may survive phagocytosis and later cause recurrence of the pet infection (8) (9). Also, phagocytes accumulating at the site of infection in large amounts may act as "drug delivery devices" to the infected focus (15). Baytril® accumulates in white blood cells at up to 100 times the corresponding plasma concentrations, killing intraphagocytic bacteria reliably (10).
Intracellular killing mechanisms are not successful in destroying all organisms phagocytized by white blood cells (8), (9). Phagocytes provide an environment in which intracellular pathogens may be sheltered from antimicrobial drugs. Surviving organisms such as staphylococci might reinfect the host or cause persistent infections despite antimicrobial therapy. Thus, the ability of a drug to reach therapeutic concentrations within the phagocytes is likely to influence the therapeutic outcome of the disease.
Baytril® has shown to concentrate in phagocytic cells. In experimental studies on canine alveolar macrophages, Boeckh et al. found concentrations of up to 100 times the corresponding plasma values. As intraphagocytic drug concentrations by far exceeded the corresponding plasma levels, it was concluded that intracellular accumulation is an active process (10).
There is a synergistic effect with the major killing mechanisms used by phagocytic cells, namely oxidative damage of the pathogens due to superoxide production (respiratory burst) (7). Baytril® has also demonstrated to synergistically utilize oxygen-dependent killing mechanisms used by phagocytes to enhance their intracellular killing ability (7). These effects on polymorph nuclear cells and macrophages as important parts of the immune system result in more effective phagocytosis and killing of pathogens at the site of infection.
On chemotactic stimulation, mobile phagocytes accumulate at the site of infection in large numbers. Cells loaded with high concentrations of active drug seem to be a reasonable vehicle for delivering Baytril® directly to the infected tissues (7). In a drug-free environment these drugs rapidly efflux from the phagocytes and act directly against pathogens. Phagocytes, therefore, were proposed to act, as the "drug delivery device" for Baytril® to the site of infection (15).
Enrofloxacin and its active metabolite are excreted in bile (70%) and urine (30%) in concentrations far exceeding the plasma levels (16). Elimination through the kidneys occurs by glomerular filtration of the non-protein-bound drug fraction and by active secretion via the organic anion transport system of the tubuli (13). Together with the excellent tissue penetration abilities of Baytril®, high therapeutic concentrations not only in urine but also in the tissues of the genitourinary tract are achieved (17).
(7) Kontos VI, Athanasiou LV: Use of enrofloxacin in the treatment of acute canine ehrlichiosis. Canine Practice 23 (3): 10-14, 1998.
(8) Lindenstruth H, Frost JW: Enrofloxacin (Baytril®) eine Alternative in der Psittakoseprophylaxe und -therapie bei importierten Psittaciden. Dtsch. tierärztl. Wschr. 100 (9): 364-368, 1993.
(9) Studdert VP, Hughes KL: Treatment of opportunistic mycobacterial infections with enrofloxacin in cats. JAVMA 201 (9): 1388-1390, 1992.
(10) Evans LM, Caylor KB: Mycobacterial lymphadenitis in a cat. Feline Practice 23 (4): 14-17, 1995.
(15) Aucoin DP: Intracellular-intraphagocytic dynamics of fluoroquinolone antibiotics: a comparative review. Suppl Compend Contin Educ Pract Vet 18 (2): 9-13, 1996.