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in veterinary medicine compared with human medicine. 18 Fluoroquinolones, including ciprofloxacin, are known CYP inhibitors 19 and have potential benefits in birds with aspergillosis, but caution must be exercised to prevent toxic drug

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in American Journal of Veterinary Research
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variety of bacterial infections. However, ciprofloxacin tablets, available in a generic formulation for people, are increasingly being used for treatment of infections in dogs. Veterinarians can legally prescribe drugs labeled for use in humans but not in

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in American Journal of Veterinary Research

conditions. Ciprofloxacin is a second-generation fluoroquinolone with good in vitro activity against common ocular bacterial pathogens (gram-negative and gram-positive) isolated from humans. 14,15 In the 2 decades since its introduction, however

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in American Journal of Veterinary Research

organisms in the genera Chlamydia, Mycoplasma ( Haemobartonella ), Mycobacterium , and Toxoplasma . 1,2 The drug (enrofloxacin and its active metabolite ciprofloxacin) is primarily excreted through the kidneys and, depending on the species, can also be

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in American Journal of Veterinary Research

a broad spectrum of activity against both gram-positive and gram-negative bacteria, with 97% of bacterial isolates from horses with bacterial ulcerative keratitis susceptible to ciprofloxacin. 3 Although an increase in resistance of bacterial

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in American Journal of Veterinary Research

Summary

Placental transfer of enrofloxacin and ciprofloxacin was evaluated, using a rabbit in situ perfusion model. A two-step infusion program was carried out to obtain steady-state maternal plasma concentrations of these drugs. For each compound, the placenta in 5 rabbits was perfused for 200 minutes with Earle's enriched bicarbonate buffer at flow rate of 1.5 ml/min. To assess reliability of the model, most of the determinants of placental transfer (maternal and fetal pH, gas balance, heart status, rectal temperature, and protein binding) were controlled. In addition, the infusion program included administration of antipyrine, a commonly used indicator of placental exchange.

Drug concentrations were measured in maternal plasma and perfusate by use of a high-performance liquid chromatographic assay. Plasma protein-binding estimation indicated no differences between the drugs. Placental clearance of the drugs was significantly (P< 0.01) different (0.88 ± 0.13 ml/min for enrofloxacin and 0.06 ± 0.02 ml/min for ciprofloxacin). These values accounted for 81 and 5%, respectively, of the placental clearance found for antipyrine.

These results indicate that caution must be taken when enrofloxacin is to be used during pregnancy, and suggest the need to extend this type of experiment to species that can be exposed to these drugs used for therapeutic or prophylactic purposes.

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in American Journal of Veterinary Research

Abstract

Objectives

To determine pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after a single IV and IM administration of enrofloxacin and tissue residues after serial daily IM administration of enrofloxacin in pigs.

Animals

20 healthy male pigs.

Procedure

8 pigs were used in a crossover design to investigate pharmacokinetics of enrofloxacin after a single IV and IM administration (2.5 mg/kg of body weight). Twelve pigs were used to study tissue residues; they were given daily doses of enrofloxacin (2.5 mg/kg, IM for 3 days). Plasma and tissue concentrations of enrofloxacin and ciprofloxacin were determined. Residues of enrofloxacin and ciprofloxacin were measured in fat, kidney, liver, and muscle.

Results

Mean (± SD) elimination half-life and mean residence time of enrofloxacin in plasma were 9.64 ± 1.49 and 12.77 ±2.15 hours, respectively, after IV administration and 12.06 ± 0.68 and 17.15 ± 1.04 hours, respectively, after IM administration. Half-life at α phase of enrofloxacin was 0.23 ± 0.05 and 1.94 ± 0.70 hours for IV and IM administration, respectively. Maximal plasma concentration was 1.17 ± 0.23 µg/ml, and interval from injection until maximum concentration was 1.81 ± 0.23 hours. Renal and hepatic concentrations of enrofloxacin (0.012 to 0.017 µg/g) persisted for 10 days; however, at that time, ciprofloxacin residues were not detected in other tissues.

Conclusions and Clinical Relevance

Enrofloxacin administered IM at a dosage of 2.5 mg/kg for 3 successive days, with a withdrawal time of 10 days, resulted in a sum of concentrations of enrofloxacin and ciprofloxacin that were less than the European Union maximal residue limit of 30 ng/g in edible tissues. (Am J Vet Res 1999;60:1377–1382)

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in American Journal of Veterinary Research

Abstract

Objective

To evaluate the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after administrations of enrofloxacin in sheep.

Design

Crossover study performed by IV and IM administrations of 2.5 mg of enrofloxacin/kg of body weight to 2 groups of 3 sheep. After a 15-day resting period, the drug administration was repeated, using the alternative route.

Animals

6 clinically normal Massese sheep of either sex.

Procedure

Blood samples were collected at suitable intervals over a 24-hour period, and plasma concentrations of enrofloxacin and its main metabolite ciprofloxacin were determined by a high-performance liquid chromatography method. Pharmacokinetic variables for both substances after IV and IM enrofloxacin administrations were calculated by use of statistical moments and were analyzed, using a crossover ANOVA.

Results

After IV administration of enrofloxacin, a rapid distribution phase was followed by a slower elimination phase. When the same dose was administered IM, enrofloxacin was rapidly and almost completely absorbed, with bioavailability of 85%. After 24 hours, the mean plasma concentration of ciprofloxacin was similar to that of the parent drug.

Conclusions

The large volume of distribution indicates that enrofloxacin is widely distributed in the body of sheep. The fraction of enrofloxacin metabolized to ciprofloxacin (35 and 55% for IV and IM administrations, respectively) suggests that, in this species, the antimicrobial activity of enrofloxacin could be attributable, at least in part, to its mam metabolite ciprofloxacin.

Clinical Relevance

IV or IM administration of 2.5 mg of enrofloxacin/kg provides plasma concentrations higher than mean inhibitory concentration for most pathogens in sheep. (Am J Vet Res 1996;57:1040–1043)

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in American Journal of Veterinary Research

Abstract

Objective—To study chondrotoxic effects of enrofloxacin (ENR) and ciprofloxacin hydrochloride (CFX) on canine and equine articular chondrocytes in culture and to compare the effects with that of cultivation in Mg2+-free medium.

Sample Population—Chondrocytes from articular cartilage of 4- and 6 -month old dogs and 2- to 4- year-old horses.

Procedure—Chondrocytes were cultivated with 10, 40, 80, and 160 μg of CFX/ml, 10, 50, 100, and 150 μg of ENR/ml, or in Mg2+-free medium. A live-to-dead test was performed to test cytotoxic effects. Morphologic changes were evaluated by electron microscopy. An attachment assay was used to test the ability of chondrocytes to adhere to collagen type- II coated-chamber slides in the presence of CFX and with Mg2+-free medium.

Results—Chondrocytes cultivated in quinolone-supplemented medium or Mg2+-free medium had a decreased ability to adhere to culture dishes. Cell shape and the actin and vimentin cytoskeleton changed in a concentration-dependent manner. These effects were not species-specific and developed with both quinolones. On day 1 of culture, adhesion of chondrocytes to collagen type II was reduced to 70 and 45% of control values in the CFX treatment and Mg2+-free treatment groups, respectively. On day 5 of culture, adhesion of chondrocytes was reduced to 45 and 40% of control values in the CFX treatment and Mg2+-free treatment groups, respectively.

Conclusion and Clinical Relevance—In vitro, chondrotoxic effects of quinolones appear to be the result of irregular integrin signaling and subsequent cellular changes. Drug concentrations leading to morphologic changes in vitro may be achieved in articular cartilage in vivo. (Am J Vet Res 2001;62:704–708)

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in American Journal of Veterinary Research

Summary

Ciprofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to 4 healthy dogs at dosage of approximately 11 and 23 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (tcf) concentrations of ciprofloxacin were measured after the first and seventh dose of each dosing regimen. The peak concentration was greatest in the serum after multiple doses of 23 mg/kg (mean ± sem; 5.68 ± 0.54 μg/ml) and least in the tcf after a single dose of 11 mg/kg (0.43 ± 0.54 μg/ml). The time to peak concentration was not influenced by multiple dosing or drug dose, but was longer for tcf (6.41 ± 0.52 hour) than for serum (1.53 ± 0.52 hour). Accumulation of ciprofloxacin was reflected by the area under the concentration curve from 0 to 12 hours after administration (AUC0→12). The AUC0→12 was greatest in the serum after multiple doses of 23 mg/kg (31.95 ± 1.90 μg·h/ml) and least in the tcf after a single dose of 11 mg/kg (3.87 ± 1.90 μg·h/ml). The elimination half-life was not influenced by multiple dosing or dose concentration, but was greater for tcf (14.59 ± 1.91 hours) than for serum (5.14 ± 1.91 hours). The percentage of tcf penetration (AUCTCF/AUCserum ) was greater after multiple doses (95.76 ± 6.79%) than after a single dose (55.55 ± 6.79%) and was not different between doses of 11 and 23 mg/kg. Both dosing regimens of ciprofloxacin resulted in continuous serum and tcf concentrations > 90% of the minimal inhibitory concentration for the aerobic and facultative anaerobic clinical isolates tested, including Pseudomonas aeruginosa.

Free access
in American Journal of Veterinary Research