Enrofloxacin is widely used in veterinary medicine and is an important alternative to treating bacterial infections, which play an important role as causes of disease and death in captive snakes. Its extralabel use in nontraditional species has been related to its excellent pharmacokinetic and antimicrobial characteristics. This can be demonstrated by its activity against gram-negative organisms implicated in serious infectious diseases of reptile species with a rapid and concentration-dependent bactericidal effect and a large volume of distribution. Pharmacokinetic parameters for enrofloxacin were investigated in seven urutu pit vipers (Bothrops alternatus), following intramuscular injections of 10 mg/kg. The plasma concentrations of enrofloxacin and its metabolite, ciprofloxacin, were measured using high-performance liquid chromatography. Blood samples were collected from the ventral coccygeal veins at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 108, and 168 hr. The kinetic behavior was characterized by a relatively slow absorption (time of maximal plasma concentration = 4.50 +/- 3.45 hr) with peak plasma concentration of 4.81 +/- 1.12 microg/ml. The long half-life during the terminal elimination phase (t1/2 lambda = 27.91 +/- 7.55 hr) of enrofloxacin after intramuscular administration, calculated in the present study, could suggest that the antibiotic is eliminated relatively slowly and/or the presence of a slow absorption in urutu pit vipers. Ciprofloxacin reached a peak plasma concentration of 0.35 microg/ml at 13.45 hr, and the fraction of enrofloxacin metabolized to ciprofloxacin was 13.06%. If enrofloxacin's minimum inhibitory concentration (MIC90) values of 0.5 microg/ml were used, the ratios AUC(e+c): MIC90 (276 +/- 67 hr) and Cmax(e+c): MIC90 (10 +/- 2) reach the proposed threshold values (125 hr and 10, respectively) for optimized efficacy and minimized resistance development when treating infections caused by Pseudomonas. The administration of 10 mg/kg of enrofloxacin by the i.m. route should be considered to be a judicious choice in urutu pit vipers against infections caused by microorganisms with MIC values < or = 0.5 microg/ml. For less susceptible bacteria, a dose increase and/or an interval reduction should be evaluated.
Crotalus atrox is one of the species of venomous snakes most commonly found in herpetological collections around the world and it is usually commercialized in the black market. Several collections have specimens but lack of the specific antivenom. We tested the toxicity of venom of adults and young snakes (2 to 3 years old) specimens of C. atrox in captivity and the para-specific neutralization provided by the antivenoms most used in Argentina. The i.p. lethal potency of the venoms were 100(95-105) μg and 43(42-45) μg/20g mouse and the indirect hemolytic activity was 7.9 (6.7-9.2) μg and 9.0(8.3-9.9) for adults and juvenile venoms. Despite the adult´s venoms lower lethal potency, these venoms were more difficult to neutralize, around 1.5 ml of antibothropic Antivenom (AB) were necessaries to neutralize 1 mg of venom in contrast to 0.54 ml required to neutralize young´s venoms. The neutralization by the Anticrotalic (AC) antivenom was despicable. The dose of AB required for the neutralization 5.0 LD 50 of young snakes was in the range of those required for the neutralization of the specific venoms, nevertheless the dose required to neutralize venom from adults was 6 fold higher. The experiments using 2LD 50 as challenge dose, showed similar results. The indirect hemolysis caused by both venoms was similarly neutralized by AB (p<0.05) while the AC did not show neutralizing activity. The myotoxicity determined by the increase of creatinquinase or by histopathology, was neutralized by both antivenoms, possibly due to the presence of myotoxins like K49 phospholipases present in this venom. Although the paraspecificity of AB has a potential use as treatment, especially in young snakes bites, the doses required in adult attacks are high. Despite AB seems to be useful for emergencies, these results suggest advantages in using specific antivenom for the treatment of these snakebites.
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