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

  • 摘要: 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。

     

    Abstract: Pharmacokinetics of florfenicol and its metabolite, florfenicol amine in red swamp crayfish (Procambarusclarkii) were investigated at the water temperature (21±1)℃ after they were given a single oral dose of 50mg/kg bodyweight(b.w.) and intra-sinus administration(i.a) of 20 mg/kg (b.w.) respectively. Four red swamp crayfish per samplingpoint were examined after treatment. Hemolymph were collected and analyzed by reversed-phase high-performanceliquid chromatography (HPLC) method and pharmacokinetic parameters were calculated by non-compartment methodof 3p97 Practical Pharmacokinetic Program software. After i.a florfenicol injection, the elimination half-life (t1/2), thevolume of distribution Vd(ss) and the total body clearance (CL) of florfenicol were 8.26h, 14.43L/kg and 1.21L·kg/hrespectively. 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 offlorfenicol amine and the distribution of florfenicol was wider in tissues of red swamp crayfish. Florfenicol was absorbedrapidly through the gastrointestinal tract but the bioavailability and metabolite rate were low by oral administration.

     

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