Abstract
Abstract The pharmacokinetics and absolute bioavailabilities of two generic formulations of enrofloxacin (ENRO- A; Enrol®: Medmac®, Amman, Jordan and ENRO- B; Syvaquinol® Syva®, Leon, Spain) 10% oral solutions were compared after single intracrop (i.c.) bolus administrations in reference to single intravenous bolus (i.v.) administration of standard ENRO at a dose of 10 mg/Kg body weight in broilers using a randomized parallel design. Plasma collected at predetermined time points up to 24 hours. Clinicochemical, hematological and histopathological alterations were also, demonstrated after repeated intracrop (i.c.) bolus administrations of the two different enrofloxacin generic preparations given at a dose regimen of 10 mg/Kg body weight for 5 consecutive days in ENRO-A and ENRO-B treated groups whereas control group was kept untreated and given water instead. Blood samples were collected from all birds on the 5th day for clinicochemical and hematological examinations. Birds were then humanely sacrificed liver, kidneys and heart were dissected out for histopathological examination. HPLC assay was used to measure concentrations of ENRO in plasma. The pharmacokinetic analysis of the C-T data was performed using non-compartmental analysis based on statistical moment theory. The maximum plasma concentrations (Cmax) for ENRO-A and ENRO-B were 1.61 ± 0.203 and 1.79 ± 0.283 μg/mL; respectively, attained at time to peak (Tmax) of 2 h. Elimination half- lives (T1/2β) were 8.391 ± 0.312 and 8.458 ± 0.906 h, respectively. While areas under plasma concentration-time curves (AUC0→∞), and systemic bioavailabilities (F %) were 12.744 ± 2.951 and 14.354 ± 2.85 mg.h/L; and 78.96 ± 6.728 and 88.94 ± 10.89 % for ENRO-A and ENRO-B; respectively. Results of safety study revealed that ENRO-A induced a significant (p<0.05) increase of the activity of alkaline phosphatase compared to ENRO-B as well as control group. Both ENRO-A and ENRO-B caused significant increases in the levels of plasma urea and creatinine concentrations compared to control (p<0.05), with higher significance in case of ENRO-A. Activity of plasma creatine kinase significantly (p<0.05) increased after ENRO-A compared to control and ENRO-B-treated groups. ENRO-A and II ENRO-B significantly (p<0.05) increased blood glucose and triglyceride levels compared to that of control. Cholesterol level was increased significantly (p<0.05) only after ENRO-B repeated administration. Parallel inflammatory and degenerative histopathological changes in the affected organs, except kidneys, have been observed. However, other metabolic parameters and hematological parameters showed insignificant changes. It could be concluded, despite that the pharmacokinetic profile of ENRO-B were better than ENRO-A. Nevertheless, data of the present study may indicate that enrofloxacin may cause organ dysfunction in broilers during the course of therapy based on clinicochemical and histopathological reasons administration of either ENRO-A or ENRO-B. However, both generics were within the FDA and EMEA bioequivalence acceptance range of 80%–125% and thus can be used as interchangeable therapeutic agents in broiler chickens. Key words:- Bioavailability; Bioequivalence; Broiler; Chicken; Enrofloxacin; Pharmacokinetics; Safety.