盐酸沙拉沙星在中华绒螯蟹体内药动学及药效学研究

Pharmacokinetics and pharmacodynamics of sarafloxacin hydrochloride in Eriocheir sinensis

研究了盐酸沙拉沙星(Sarafloxacin hydrochloride)在中华绒螯蟹(Eriocheir sinensis)雄蟹和雌蟹体内药动学,检测了盐酸沙拉沙星对致病性气单胞菌的最小抑菌浓度(MIC),建立了药动/药效(PK/PD)关系。盐酸沙拉沙星以30 mg.kg-1单剂量口灌给药中华绒螯蟹,雌蟹和雄蟹血浆沙拉沙星浓度-时间关系曲线均符合一级吸收的二室开放动力学模型。雌蟹和雄蟹血药达峰时间(Tmax)为4 h,达峰浓度(Cmax)分别为5.619±1.192 mg.L-1和7.775±1.426 mg.L-1。沙拉沙星在雌蟹和雄蟹体内分布广泛,其表观分布容积(Vd)分别为3.801 L.kg-1和2.871 L.kg-1;消除半衰期(t1/2β)分别为51.982 h和55.956 h,总体清除率(CLs)为0.138 L.(kg.h)-1和0.087 L.(kg.h)-1,曲线下面积(AUC)分别为209.1 mg.(L.h)-1和325.5 mg.(L.h)-1。中华绒螯蟹扣蟹致病菌嗜水气单胞菌HX1b1、维氏气单胞菌CMX313和CMX4对盐酸沙拉沙星的最小抑菌浓度分别为0.5μg.mL-1、0.25μg.mL-1和0.25μg.mL-1。以30 mg.kg-1单剂量给药,嗜水气单胞菌HX1B1的Cmax/MIC值分别为15.55(雄蟹)和11.24(雌蟹)、AUC0-24/MIC值分别为197(雄蟹)和145.4(雌蟹),维氏气单胞菌CMX313和CMX4的Cmax/MIC值分别为31.1(雄蟹)和22.48(雌蟹)、AUC0-24/MIC值分别为394(雄蟹)和290.8(雌蟹)。由此可见,盐酸沙拉沙星在雌雄蟹体内的药动学数据有一定差异,但不是很大。以30 mg.kg-1剂量拌料给药,即可以有效防治上述气单胞菌引起的细菌性疾病。

The pharmacokinetics of sarafloxacin hydrochloride in Chinese Mitten Crab, Eriocheir sinensis, was investigated following oral administration. The minimum inhibitory concentrations of sarafloxacin hydrochloride on the pathogenic Aeromonas were detected. The Pharmacokinetics/pharmacodynamics （PK/PD） parameters were calculated. The hemolymph sarafloxacin hydrochloride concentration vs. time after oral administration for male and female crabs were best described by a two-compartment model with first absorption. The peak time （Tmax） for male and female crabs were 4 h, and the peak concentration （ Cm~） were 5. 619 ＋ 1. 192 mg ~ L-1 and 7.775_＋1.426 rag＂ L-1, respectively, the apparent volume of distribution （Vd） were 3. 801 L. kg-1 and 2. 871 L ~ kg-1 , respectively. Sarafloxacin was widely distributed in the male and female crabs. The elimination half-time （ tl/=~ ）, body clearance （ CLs ） and area under the concentration-time curve （AUC0.t ） for male crabs were 51. 982 h, 0. 138 mL ~ （kg ~ h）-I and 209. 1 mg ~ （L ~ h）-l, respectively. The corresponding value for female crabs were 55.956 h, 0.087 mL ~ （kg ~ h） -1 and 325.5 mg ~ （L ~ h） -1, respectively. The minimum inhibitory concentration （MIC） of sarafloxacin on the pathogenic Aeromonas hydrophila HXlbl, Aeromonas verortii CMX313 and CMX4 from Eriocheir sinensis were 0.5 I^g ＂ mL-I , 0.25 p.g ~ mL-1 and 0.25 Ixg ~ mL-1 , respectively. The Cr, ax/MIC of strain HXlbl on male and female crabs were 15.55 and 11.24, respectively, and the AUCo-24/MIC were 197 and 145.4, respectively. The Cmax/MIC of strains CMX313 and CMX4 were 31.1 and 22.48, respectively, and the AUCo_24/MIC were 394 and 290.8, respectively. Results showed that a dosage of 30 mg ~ kg-1 by medicated feed can effectively combat bacterial diseases caused by the Aeromonas.