氟苯尼考及氟苯尼考胺在克氏原螯虾体内药物代谢动力学

PHARMACOKINETICS OF FLORFENICOL AND ITS METABOLITE,FLORFENICOL AMINE,IN RED SWAMP CRAYFISH,PROCAMBARUS CLARKII

研究不同给药方式下,氟苯尼考及其代谢产物氟苯尼考胺在克氏原螯虾体内的药动学特征。在水温为(21±1)℃条件下,分别给予20 mg/kg体重单剂量血窦注射或50 mg/kg体重单剂量口灌给药,并于0.083、0.25、0.5、1、2、3、4、6、8、12、18、24和36h时间点采集血淋巴,运用反相色谱法检测血淋巴中氟苯尼考及氟苯尼考胺的浓度,采用3p97软件的非房室模型统计矩方法分析药时数据。结果表明:血窦给药后,氟苯尼考的消除半衰期(t1/2)、表观分布容积[Vd(ss)]、总体清除率(CL)分别为8.26h、14.43 L/kg、1.21 L/kg.h,氟苯尼考胺消除半衰期和代谢率(MR)分别为20.28h、9.3%;口灌给药后,氟苯尼考达峰浓度(Cmax)、达峰时间(Tmax)、消除半衰期、生物利用度(F)分别为2.49 mg/kg、1.0h、10.01h、21.6%,氟苯尼考胺的消除半衰期和代谢率分别为16.0h、37.5%。氟苯尼考在克氏原螯虾体内的消除比氟苯尼考胺快,并能广泛地分布于身体各组织中;氟苯尼考在胃肠中吸收迅速,但其生物利用度不高,代谢率低。

Pharmacokinetics of florfenicol and its metabolite,florfenicol amine in red swamp crayfish（Procambarus clarkii） were investigated at the water temperature（21±1）°C after they were given a single oral dose of 50mg/kg body-weight（b.w.） and intra-sinus administration（i.a） of 20 mg/kg（b.w.） respectively.Four red swamp crayfish per sampling point were examined after treatment.Hemolymph were collected and analyzed by reversed-phase high-performance liquid chromatography（HPLC） method and pharmacokinetic parameters were calculated by non-compartment method of 3p97 Practical Pharmacokinetic Program software.After i.a florfenicol injection,the elimination half-life（t1/2）,the volume of distribution [Vd（ss）] and the total body clearance（CL） of florfenicol were 8.26h,14.43L/kg and 1.21L.kg/h respectively.The t1/2 and metabolic rate（MR） of florfenicol amine were 20.28h and 9.3%.After oral administration（o.a） of florfenicol,the Cmax,Tmax,t1/2 and bioavailability（F） of florfenicol were 2.49mg/kg,1.0h,10.01h,21.6% respectively.The t1/2 and MR of florfenicol amine were 16.0h,37.5%.The elimination rate of florfenicol was quicker than that of florfenicol amine and the distribution of florfenicol was wider in tissues of red swamp crayfish.Florfenicol was ab-sorbed rapidly through the gastrointestinal tract but the bioavailability and metabolite rate were low by oral administration.