PHARMACOKINETIC PROFILE OF ENROFLOXACIN AND THE METABOLITE CIPROFLOXACIN AFTER INTRACOELOMIC ADMINISTRATION IN TORTOISES (TESTUDO HERMANNI)

INTRODUCTION Enrofloxacin (E) belongs to the fluoroquinolone class of antibiotics. It is commonly used in a variety of reptile species due to its wide spectrum of efficacy, partly due to its formation of an active metabolite ciprofloxacin (C). The pharmacokinetics of E following various routes of administration have been investigated in different species of turtles and tortoises with plasma concentrations of E and C showing a wide disposition variability [1, 2]. This underlines the importance of conducting pharmacokinetic studies for individual animal species. Several PK/ PD indices such us Cmax/MIC and AUC0–24/MIC have been included in the present study to evaluate the clinical efficacy of E. The aim of this study was to evaluate the pharmacokinetics of E and C after a single intracoelomic injection of 10 mg kg 1 of E in 9 tortoises (Testudo hermanni). MATERIAL AND METHODS The study protocol was approved by the University of Pisa’s ethics committee for animal welfare and transmitted to the Italian Ministry of Health. E as the commercial injectable solution (Baytril 25 mg ml 1, Bayer, Milan Italy), was diluted with saline to 10 mg ml 1 and given as a 10 mg kg 1 bolus by intracoelomic injection in the left prefemoral fossa. RESULTS AND CONCLUSION No adverse effects at the point of injection and no behavioural or health alterations were observed in the animals during or after the study. Blood samples were collected at scheduled times and analyzed using a validated HPLC method. Plasma concentration of E was quantifiable in all subjects up to 240 h, while C was detected in all subjects up to 120 h. The Cmax(s) of E and C were 8614 1116 ng ml 1 obtained at 2.19 h and 605 43 ng ml 1 obtained at 4.23 h, respectively. In the present study considering a bacterium with a MIC value of 0.5 lg ml 1, the Cmax/MIC ratio of E was 17.23 and the average AUC0–24/MIC ratio was higher (132.78) than the requested therapeutic value. In contrast, Cmax/MIC ratio and AUC0–24/MIC ratio of C were below the target ranges. These results could be due to the limited extent to which C is produced in reptiles (<15%). It has been postulated that this minimal presence of C could be due to the slow metabolism of turtles and tortoises. In fact, cytochrome P450 3A, the enzyme that metabolizes E to C, has been found to be poorly expressed in reptiles [3]. In conclusion, administration of 10 mg kg 1 of E via the intracoelomic route in Hermann’s tortoises appeared safe and produced optimal pharmacodynamic parameters.