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About Baytril

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• Can Baytril be given to young cats?

  It is well known that Baytril like other fluoroquinolones can cause cartilage lesions when administered during the growing phase to young dogs. In contrast to dogs, cartilage lesions could not be demonstrated in growing cats from two to ten months of age, even when they were treated at doses of up to 25 mg/kg b.w. for a maximum of 30 days (1).

  It can be concluded that Baytril can safely be used at the recommended dose in adult and in young cats as well.

  1. Altreuther P: Safety and tolerance of enrofloxacin in dogs and cats. Proceedings of the First International Baytril Symposium Bonn, 15 -19, 1992.

• Why should Baytril not be given to animals suffering from epilepsy?

  The recommendation not to treat animals (dogs) with CNS disorders, e.g. epilepsy, is a matter of precaution, which is valid for all fluoroquinolones. It has been suggested that these drugs competitively inhibit receptor binding of gamma-aminobutyric acid (GABA), which is an inhibitory transmitter in the CNS (1). Probably epileptic animals are more susceptible to quinolones compared to non epileptic individuals. Structural similarities of substituents of some quinolones at the C7-position with the binding region of the GABA molecule may be the reason for this phenomenon (2).

  For Baytril no noteworthy effects on the CNS of mice and rats have been observed. There is no indication of central nervous effects in non-epileptic dogs and cats as well, when treated at the recommended therapeutic doses of Baytril.

  1. Hooper DC, Wolfson JS: in Hooper and Wolfson: Quinolone Antimicrobial Agents, chapter 26: Adverse effects. 489 - 512, 1993.
  2. Brown SA: Fluoroquinolones in animal health. JVet Pharmacol Therapy 19: 1 - 14, 1996.

• Fluoroquinolones may interact with NSAIDs. Is that also valid for Baytril?

  Convulsions have been reported among several human patients receiving both enoxacin (a quinolone for use in human medicine) and fenbufen (a non-steroidal antiinflammatory drug - NSAID). It could be shown that fluoroquinolones inhibit the binding of gamma-aminobutyric acid (GABA) to its brain receptor (see also question about epilepsy). Fenbufen and its metabolite obviously enhances the effect of fluoroquinolones on inhibiting GABA receptor binding (1).

  In toxicology studies on mice Baytril has been given concurrently with different NSAIDs used in veterinary medicine. Although very high doses of enrofloxacin (500 mg/kg b.w.) have been given, an increase of acute toxicity could only be observed with butylscopolamine (Buscopanâ). At therapeutic doses, however, no such side effects have been observed.

  As a result of these studies, restrictions of concurrent use of Baytril and NSAIDs has been withdrawn from the label.

  1. Nix D in Hooper and Wolfson: Quinolone Antimicrobial Agents, Chapter 11: Drug-drug interactions with fluoroquinolone antimicrobial agents. 245 - 258, 1993.

• Fluoroquinolones can influence theophyllin metabolism. How should the dose be adapted in case enrofloxacin and theophyllin have to be administered simultaneously?

  Theophylline, a methylxantine drug, is used in veterinary medicine for bronchodilatation and to increase diuresis. Although the mechanism is not completely clear it has been shown on humans and animals that fluoroquinolones interact with theophylline pharmacokinetics by decreasing its metabolic clearance. Selective inhibition of specific isoenzymes of the cytochrome P-450 pathway by quinolones seems to be one of the major mechanisms.

  In a study on beagle dogs INTORRE et al. (1) examined the interaction of enrofloxacin given simultaneously with theophylline. Results of this study indicate that enrofloxacin treatment lowered the mean theophylline clearance by 43 %, compared to the theophylline clearance before administration of the quinolone.

  It has been recommended to lower the dose of theophyllin in case dogs have to be treated with enrofloxacin at the same time in order to avoid side effects, such as cardiocirculatory or central nervous symptoms of theophylline overdosing. Therapeutic plasma drug monitoring may help to avoid theophylline toxicity. Small animals may not develop clinical signs until plasma concentrations of this drug reach 40 - 60 mg/ml in dogs and 40 mg/ml in cats (2).

  As a rule of thumb for the clinician it has been recommended to reduce the general dose of theophylline by 50% in human patients undergoing concurrent fluoroquinolone therapy (3).

  1. Intorre L, Mengozzi G, Maccheroni M, Bertini S, Soldani G: Enrofloxacin-theophylline interaction: influence of enrofloxacin on theophylline steady-state pharmacokinetics in the beagle dog. J.vet.Pharmacol.Therap. 18, 352 - 356, 1995.
  2. Boothe DM: Drug therapy for respiratory tract infections. Bayer Selected Proceedings TNAVC: 10 - 19, 1998.
  3. Nix D in Hooper and Wolfson: Quinolone Antimicrobial Agents, Chapter 11: Drug-drug interactions with fluoroquinolone antimicrobial agents, 245 - 258, 1993.

• Is there any evidence of Baytril being nephrotoxic?

  Quinolones are not primarily nephrotoxic. Nephrotoxicity and crystalluria have only been observed in rare cases in humans undergoing therapy with a limited number of quinolones. Crystalluria has been associated with high doses and alkaline conditions (pH 7-9) in the urine, where solubility of these drugs is lowest (1).

  Subchronic feeding studies with enrofloxacin on laboratory species and dogs revealed no evidence of kidney damage or intrarenal crystallisation, although daily doses far above the therapeutic range of Baytril (in dogs up to 52 mg/kg b.w.) were administered (2).

  As a matter of precaution, however, it has been recommended to rehydrate exsiccated patients adequately before quinolone therapy is initiated (3).

  1. Kuhlmann J, Schaefer HG, Beermann D in Kuhlmann J, Dalhoff A, Zeiler HJ: Quinolone Antibacterials, Chapter 11: Clinical pharmacology, 339 - 406, 1998.
  2. Altreuther P: Safety and tolerance of enrofloxacin in dogs and cats. Proceedings of the First International Baytril Symposium Bonn, 15 -19, 1992.
  3. McKeller QA: Clinical relevance of the pharmacologic properties of fluoroquinolones. Suppl Compend Contin Educ Pract Vet Vol. 18(2), 14 - 21, 1996.

• What is the best time to applicate Baytril, before feeding or just added to the food?

  In a study performed by KÜNG et al. plasma drug kinetics of Baytril have been examined in dogs receiving dry food and canned food under different feeding regimens. Results of this study indicate that Cmax values and area under the time-concentration curve (AUC) of enrofloxacin were significantly higher in dogs receiving canned food compared to dry food, independently of the feeding time. It has also been demonstrated that enrofloxacin in dogs receiving canned food had the highest bioavailability, in case Baytril tablets were administered one hour before feeding (1).

  Of course it may not be wise to change the type of food the animal is used to in case it gets ill. In any case, however, dogs receiving medication one hour before feeding will have the best drug exposure to Baytril, when oral administration is possible.

  1. Küng K, Wanner M: Einfluß zweier verschiedener Futter auf die Pharmakokinetik von oral appliziertem Baytrilâ (Enrofloxacin) beim Hund. Kleintierpraxis 38, 95 - 102, 1993.

• Why should fluoroquinolones be applicated once daily instead of twice daily as recommended before?

  As demonstrated by MEINEN et al. the killing activity of fluoroquinolones against E.coli and staphylococci is concentration-dependent (1). In this study the total dose and not the dose frequency was significant in determinig the therapeutic efficacy of enrofloxacin. This means the higher the plasma drug concentration (Cmax) the faster and more effective antimicrobial killing is achieved. It was also found that time above the MIC was not significant in determining the efficacy of this drug. Similar findings for other bacteria species relevant for small animal practice ( Pasteurella, Pseudomonas, Salmonella) have been made by WETZSTEIN et al.(2).

  From these findings it can be concluded that once daily application of the total dose of fluoroquinolones will have greater therapeutic effect compared to treatment regimens where the dose is divided into two applications.

  1. Meinen JB, McClure JT, Rosin E : Pharmacokinetics of enrofloxacin in clinically normal dogs and mice and drug pharmacodynamics in neutropenic mice with Escherichia coli and staphylococcal infections. Am. J. Vet. Res., 56, 1219 - 1224, 1995.
  2. Wetzstein HG, De Jong A : In vitro bactericidal activity and postantibiotic effect of fluoroquinolones used in veterinary medicine. Suppl Compend Contin Educ Pract Vet 18 (2), 22 - 29, 1996.

• Is it possible to use ciprofloxacin from human medicine instead of Baytril in dogs?

  It is well known that fluoroquinolones are drugs with concentration-dependent antimicrobial efficacy. Aim of therapy therefore should be to achieve plasma peak concentrations (Cmax),which are as high as possible.

  In a recent study on dogs HEINEN compared plasma drug concentrations after single oral application of 5 mg/kg b.w. Baytril® and 5 mg/kg b.w. Ciprobay® respectively (bioassay data). Mean Cmax values after application of Baytril were 1.90 mg/ml, whereas Ciprobay reached a mean Cmax in plasma of 0.52 mg/ml, which is only 27% of the concentration when Baytril was administered (1). It has been postulated that the intestinal absorption rate of enrofloxacin is superior to ciprofloxacin in the species dog.

  Compared to Baytril® Ciprobay® therefore is not a suitable alternative for therapy of canine patients,.

  1. Heinen E : Comparative pharmacokinetics of enrofloxacin and difloxacin as well as their main metabolites in dogs. Suppl Compend Contin Educ Pract Vet, 21, 12 (M), 12 - 18, 1999.

• Is it true that Baytril is less effective at lower urine pH when treating urinary tract infections?

  It is well known that some quinolones have less in vitro antimicrobial activity at lower pH levels. In a comparison of different quinolones from human medicine ciprofloxacin, norfloxacin and different others showed lower activity against E.coli and Staph.aureus at pH 4.8 compared to pH 6.8 in the culture medium (x).

  In another publication from FERNANDES the in vitro activity of norfloxacin, pefloxacin, ciprofloxacin, ofloxacin and difloxacin against different bacteria species was compared at pH levels of 6.5, 7,2 and 8,0. Here norfloxacin, ciprofloxacin and ofloxacin in fact showed somewhat lower activity at low pH, whereas pefloxacin and difloxacin were not adversely affected to a significant degree (xi). However, it has to be pointed out that the general antimicrobial activity of pefloxacin and difloxacin in general was much lower compared to ciprofloxacin.

  It remains questionable whether the findings mentioned above have any clinical relevance, because fluoroquinolones in general reach very high concentrations in the urine and a diminished activity at lower pH-vales will be compensated this way (xii).

  Although similar in vitro data are not available for Baytril (enrofloxacin) deficits in clinicial efficacy are unlikely, because peak concentrations of active drug in the urine exceed 200 mg/ml, which is far beyond the MICs of all relevant bacteria commonly involved in urinary tract infection (xiii).

  Above that, when cystitis is present the urine pH of dogs and cats, which normally is slightly acidic, becomes basic when bacteria metabolize urea into ammonia (NH3).

  • 

  5. Eliopoulos GM, Eliopoulos CT in Hooper and Wolfson: Quinolone Antimicrobial Agents, chapter 8: Activity in vitro of the quinolones, 161 - 193, 1993.
  6. Fernandes PB: Mode of action, and in vitro and in vivo activities of the fluoroquinolones. J Clin Pharmacol 28: 156-168, 1988.
  7. Norrby SR in Hooper and Wolfson: Quinolone Antimicrobial Agents, chapter 13: Treatment of urinary tract infections with quinolone antimicrobial agents, 273-283, 1993.
  8. Monlouis JD, DeJong A, Limet A, Richez P: Plasma pharmacokinetics and urine concentrations after oral administration of enrofloxacin to dogs. Proceedings 7th EAVPT Congress, Madrid: J vet Pharmacol Therap 20 (Suppl 1): 61 - 63, 1997