| Enrofloxacin is a synthetic third-generation fluoroquinolone. It has a broad spectrum of activity against many pathogens of veterinary importance. However, there were few reports about the research on the technology of pharmacokinetics of enrofloxacin perfusate in sows. This study was designed to determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after intravenous and intrauterine administrations of enrofloxacin to sows, and evaluated the safety of enrofloxacin perfusate.The pharmacokinetics of enrofloxacin perfusate in sows:This study was designed to determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after intravenous and intrauterine administrations of enrofloxacin to sows, and evaluate the feasibility to promote the drug concentration in target tissues by changing the administration route. 16 cross-bred(Landrace×Yorkshire) healthy, adult, non-lactating sows at 2 and 3 years of age, were used. The sows were randomly divided into two groups. The first groups was administered with enrofloxacin injection by intravenous route, at a single dose of 2.5 mg·kg-1 body weight; whereas the second group was administered with enrofloxacin solution by intrauterine administration at a dose of 50 m L for each sow. Enrofloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. A non-compartmental analysis of drug plasma concentration vs. time profiles was performed with pharmacokinetic modeling using Winnonlin software. Concentrations of the active metabolite ciprofloxacin were not detected in any samples. Following intravenous administration, the main pharmacokinetic parameters were as follows: t1/2,(21.71±1.66) h; Vd,(1.89±0.33) L·kg-1; Cl,(60.18±8.92) m L·h-1·kg-1; AUC0-t,(39.94±5.75) mg·h·L-1, AUC0-?(42.32±6.03) mg·h·L-1. The absorption of enrofloxacin was rapid and well absorbed after intrauterine administration, with t1/2 of 28.55±4.94 h, Tmax of 3.19±1.46 h, Cmax of 1.61±0.20 mg·L-1, AUC0-t of 49.06±5.18 mg·h·L-1, AUC0-? of 53.55±5.84 mg·h·L-1. The absolute bioavailability(F) was 63.15%. Concentrations of the active metabolite ciprofloxacin were not detected in any samples. The results showed that the sows can absorb enrofloxacin well by way of intrauterine administration, with slowly eliminated and high bioavailability. And the effect on body after intrauterine administration should be considered.The safety evaluation of enrofloxacin perfusate in sows: Twenty adult healthy sows weighted 204.52±25.85 kg were devided into groups randomly(n=5, each group). Sows in different group were given doses enrofloxacin 0 m L(control), 50 m L(recommend dose), 150 m L(three times of recommend dose), 250 m L(five times of recommend dose) by intrauterine administration for nine days. Its safety was evaluated through clinical observation, means of blood routine, indexes of blood biochemical inspection on the day 0, 7, 14 after intrauterine administration, pathological anatomy and histological observation. Among four groups, the clinical observations were normal, so did the means of blood routine(WBC?RBC?HGB?HCT?MCV?MCH?MCHC and PLT, P>0.05). Indexes of TBIL, Mg and LDH in group of three-time and five-time recommended doses were significantly increased on day 7(P<0.05), but they became normal again on day 14. Other indexes were no significance(P>0.05). Moreover, there were several hepatic petechias in the group of five-time recommended dose in pathological anatomy and histological observation. The results shows that recommend dose of enrofloxacin perfusate had no significant effect on blood and blood biochemical indexes, while no significant change appeared in tissue pathology. However, high-dose enrofloxacin may impair the liver. |
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