Clinical Pharmacology

Marbofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract following oral administration to fasted animals. Divalent cations are generally known to diminish the absorption of fluoroquinolones. The effects of concomitant feeding on the absorption of marbofloxacin have not been determined. (See Drug Interactions.) In the dog, approximately 40% of an oral dose of marbofloxacin is excreted unchanged in the urine1. Excretion in the feces, also as unchanged drug, is the other major route of elimination in dogs. Ten to 15% of marbofloxacin is metabolized by the liver in dogs.

In vitro plasma protein binding of marbofloxacin in dogs was 9.1% and in cats was 7.3%. In the cat, approximately 70% of an oral dose is excreted in the urine as marbofloxacin and metabolites with approximately 85% of the excreted material as unchanged drug. Pharmacokinetic parameters related to intravenous dosing were estimated in a study of 6 healthy adult beagle dogs, and are summarized in Table 1. The absolute bioavailability following dosing of oral tablets to the same animals was 94%.

Marbofloxacin plasma concentrations were determined over time in healthy adult beagle dogs (6 dogs per dosage group) following single oral doses of 1.25 mg/lb or 2.5 mg/lb. Absorption of orally administered marbofloxacin increases proportionally over the dose range of 1.25 to 2.5 mg/lb. Marbofloxacin plasma concentrations were determined over time in 7 healthy adult male cats following a single oral dose of 2.5 mg/lb. Plasma pharmacokinetic parameters following oral dosing of dogs and cats are summarized in Figures 2 and 3 and in Table 2. Based on the terminal elimination half-life and the dosing interval, steady-state levels are reached after the third dose and are expected to be approximately 25% greater in dogs and 35% greater in cats than those achieved after a single dose. Marbofloxacin is widely distributed in canine tissues. Tissue concentrations of marbofloxacin were determined in healthy male beagle dogs (4 dogs per time period) at 2, 18 and 24 hours after a single oral dose (1.25 or 2.5 mg/lb) and are summarized in Tables 3a and 3b.

 

Figure 2: Mean plasma concentrations (µg/mL) following single oral administration of marbofloxacin to adult beagle dogs at dosages of 1.25 mg/lb or 2.5 mg/lb.

* See Table 4 in Microbiology section for MIC data.

Figure 3: Mean plasma concentrations (µg/mL) following single oral administration of marbofloxacin to adult cats at a dosage of 2.5 mg/lb.

* See Table 5 in Microbiology section for MIC data.

 

Microbiology: The primary action of fluoroquinolones is to inhibit the bacterial enzyme, DNA gyrase. In susceptible organisms, fluoroquinolones are rapidly bactericidal at relatively low concentrations. Marbofloxacin is bactericidal against a broad range of gram-negative and gram-positive organisms. The minimum inhibitory concentrations (MICs) of pathogens isolated in clinical field studies performed in the United States were determined using National Committee for Clinical Laboratory Standards (NCCLS) standards, and are shown in Tables 4 and 5.