盐酸沙拉沙星在蛋鸡体内的组织动力学及残留的研究
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摘要
盐酸沙拉沙星是一种动物专用的氟喹诺酮类药物。本文以高效液相色谱法（HPLC）
为定量手段，研究了盐酸沙拉沙星在成年健康蛋鸡血液和组织中的经时过程以及盐酸沙
拉沙星在组织中的残留。并运用回归分析的方法，研究血液和组织间含药量的动态相关
关系，建立组织含药量的间接预测方程。由单剂量给药参数，算出多剂量给药参数，为
临床应用提供理论依据。
采用MCP-KP自动化药动学分析程序对数据进行分析。药动学结果表明：蛋鸡单
剂量口服盐酸沙拉沙星后（10mg/kg），血液经时过程符合一级吸收一室开放式模型，其
理论方程为：C_b=1.036（e~(-0.1735t)-e~(-2.057t)），主要动力学参数t_(1/2k)3.793hrs、t_(max)1.5807hrs、
c_(max)0.7429μg/ml、AUC5.3790μg/ml.h。
组织中的盐酸沙拉沙星的经时过程：心脏符合一级吸收三项指数方程，理论方程
为：C_h=0.1455e~(-0.0243t)+2.484e~(-0.54403t)-2.629e~(-0.8617t)，主要动力学参数t_(1/2B)7.765hrs、t_(1/2a)1.6027
hrs、t_(max)1.6826hrs、c_(max)0.5129μg/ml、AUC9.0265μg/ml.h。
肾脏符合一级吸收三项指数方程，理论方程为：C_k=1.703e~(-0.126t)+0.3283e~(-0.2111t)-
2.0312e~(-0.4976t)，主要动力学参数t_(1/2B)40.26hrs，t_(1/2a)4.418hrs、t_(max)1.9855hrs、c_(max)0.9090μ
g/ml、AUC10.894μg/ml.h。
肝脏符合一级吸收二项指数方程，理论方程为：C_l=6.732（e~(-0.18103t)-e~(-0.1108t)），主要
动力学参数t_(1/2k)3.1587hrs、t_(max)1.9764hrs、c_(max)3.737μg/ml、AUC31.354μg/ml.h。
肌肉符合一级吸收二项指数方程，理论方程为：C_m=0.9188（e~(0.1579t)-e~(-0.2014t)），主要
动力学参数t_(1/2k)4.124hrs、t_(max)3.5679hrs、c_(max)0.6956μg/ml、AUC5.3269μg/ml.h。
组织动力学研究结果表明：盐酸沙拉沙星的组织含药量，以肝脏最高，肾脏、肌
肉次之，心脏最低，但均超过多数敏感菌株的最低抑菌浓度。根据血清和组织中药物消
除规律推算出药物浓度降至0.01μg/ml所需时间，血液、心脏、肝脏、肾脏、肌肉分
别为25.58、49.83、32.63、160.02、29.43（hrs），以肾脏中药物残留时间长。
对血药浓度与组织药物浓度进行一元线性回归、多元线性回归和一元曲线回归分
析。结果表明，这三种分析方法均能较好地研究血药浓度与组织药物浓度的动态变化规
律，且曲线回归在分析的整体性及准确性方面优于直线回归。利用各种回归方程，可达
到间接预测组织含药量的目的。
Sarafloxacin Hydrochloride is one of floroquinolones only used for animals infectious
diseases.In this thesis, the pharmacokinetics process of sarafloxacin Hydrochloride of chicken
and the residue in tissue of chicken are studied by using the (High performance liquid
chromatography,HPLC) procedure. The dynamic interrelated relationship of the drug level
between serum and tissue were analyzed by the use of the regression analysis, and the indirectly
predictive equation about the drag concentration in tissue is established.
The data were analyzed with the Pharma~olinetics computer program MCP-KP.
Phamiacolinetics show that the blood concentration-time course can be described with the first
compartment open model with the first order absorption alter oral administration( 10mg/kg) .Its
theoretical equation was as follows: CbI .036 (eI735t - e2057t), its main pharmacokinetics
parameters t1,.3.793his. t...I.5807brs.. c0.7429 i g/ml.. AUC5.3790 i g/ml. h0
The kinetics process Sarafloxacin Hydrochloride in tissues: the heart concentration -time
(C1-T) data of Sarafloxacin Hydrochloride was best described by a triexponential equation
with flint order absorption.Its theoretical equation was as follows: Ch = 0.1455e0 43+2.484&
OS44O3L2629e lS6I7t its main pharmacokinetics parameters t117.765hrs t111 .6027
tl.6826 hrs c0.5129 j.i g/ml . AUC9.0265 .t g/ml. h0
The heart concentration -time (C-T3 data of Sarafloxacin Hydrochloride was best
described by a triexponential equation with first order absorption.Its theoretical equation was as
-O.12&-02111t -04976t
follows: Ck = I .703e +0.3283e -2.031 2e , its main pharmacokinetics parameters
t1, 40.26 hrs.. t4.418hrs. t 1.9855 hrs c0.9090 i g/ml., AUC1O.894 .t g/ml. h
The liver concentration -time (C1-T3 data of Sarafloxacin Hydrochloride was best
described by a biexponential equation with first order absorption.Its theoretical equation was as
-018103t .O1IO&
follows: C1= 6.732(e - e ), its main pharmacokinetics parameters tl,2k3.1587hIS
t1,1.9764hrs. c3.737 j.t gin 1.. AUC31.354 5.1 giml. h.
The muscle concentration -time (C1-T1) data of Sarafloxacin Hydrochloride was best
described by a biexponential equation with first order absorption.Its theoretical equation was as
follows: Cm 0.91 88(e0157 - eO2OI4t) its main pharmacokinetics parameters t112k4. l24hrs-.
t,3.5679hrs.. c0.6956 ji giml.. AUC5.3269 g/ml. hrs.
Tissue phannacokinetics indicates Sarafloxacin Hydrochloride concentration in tissue is the
highest for liver, and lower for kidney and muscle, and the lowest for the heart. And the
residue time of drug in kidney is longer than that in the other tissue..According to the
elimination regularity of serum. heart liver., kidney and muscle,the time taken by the drag
concentration dropping to 0.OIug/ml is calculated.They were 5.58(hrs), 49.83(hrs),
32.63brs) ,160.02(hrs), 29.43(hrs).
The drug concentration in serum and tissue is analyzed by the use of the liner regression
equation in one unknow and multi-unkow, and the curvilinear regression equation in one
unkow. The results indicate that the dynamic variation regularity of the drug concentration in
serum and tissue can be better studied with this two analysis method, and the curvilinear
regression is better than the linear one in entirety and accuracy.The purpose of prediction the
drug concentration in tissue indirectly is achieved by the use of various regression equations.
为定量手段，研究了盐酸沙拉沙星在成年健康蛋鸡血液和组织中的经时过程以及盐酸沙
拉沙星在组织中的残留。并运用回归分析的方法，研究血液和组织间含药量的动态相关
关系，建立组织含药量的间接预测方程。由单剂量给药参数，算出多剂量给药参数，为
临床应用提供理论依据。
采用MCP-KP自动化药动学分析程序对数据进行分析。药动学结果表明：蛋鸡单
剂量口服盐酸沙拉沙星后（10mg/kg），血液经时过程符合一级吸收一室开放式模型，其
理论方程为：C_b=1.036（e~(-0.1735t)-e~(-2.057t)），主要动力学参数t_(1/2k)3.793hrs、t_(max)1.5807hrs、
c_(max)0.7429μg/ml、AUC5.3790μg/ml.h。
组织中的盐酸沙拉沙星的经时过程：心脏符合一级吸收三项指数方程，理论方程
为：C_h=0.1455e~(-0.0243t)+2.484e~(-0.54403t)-2.629e~(-0.8617t)，主要动力学参数t_(1/2B)7.765hrs、t_(1/2a)1.6027
hrs、t_(max)1.6826hrs、c_(max)0.5129μg/ml、AUC9.0265μg/ml.h。
肾脏符合一级吸收三项指数方程，理论方程为：C_k=1.703e~(-0.126t)+0.3283e~(-0.2111t)-
2.0312e~(-0.4976t)，主要动力学参数t_(1/2B)40.26hrs，t_(1/2a)4.418hrs、t_(max)1.9855hrs、c_(max)0.9090μ
g/ml、AUC10.894μg/ml.h。
肝脏符合一级吸收二项指数方程，理论方程为：C_l=6.732（e~(-0.18103t)-e~(-0.1108t)），主要
动力学参数t_(1/2k)3.1587hrs、t_(max)1.9764hrs、c_(max)3.737μg/ml、AUC31.354μg/ml.h。
肌肉符合一级吸收二项指数方程，理论方程为：C_m=0.9188（e~(0.1579t)-e~(-0.2014t)），主要
动力学参数t_(1/2k)4.124hrs、t_(max)3.5679hrs、c_(max)0.6956μg/ml、AUC5.3269μg/ml.h。
组织动力学研究结果表明：盐酸沙拉沙星的组织含药量，以肝脏最高，肾脏、肌
肉次之，心脏最低，但均超过多数敏感菌株的最低抑菌浓度。根据血清和组织中药物消
除规律推算出药物浓度降至0.01μg/ml所需时间，血液、心脏、肝脏、肾脏、肌肉分
别为25.58、49.83、32.63、160.02、29.43（hrs），以肾脏中药物残留时间长。
对血药浓度与组织药物浓度进行一元线性回归、多元线性回归和一元曲线回归分
析。结果表明，这三种分析方法均能较好地研究血药浓度与组织药物浓度的动态变化规
律，且曲线回归在分析的整体性及准确性方面优于直线回归。利用各种回归方程，可达
到间接预测组织含药量的目的。
Sarafloxacin Hydrochloride is one of floroquinolones only used for animals infectious
diseases.In this thesis, the pharmacokinetics process of sarafloxacin Hydrochloride of chicken
and the residue in tissue of chicken are studied by using the (High performance liquid
chromatography,HPLC) procedure. The dynamic interrelated relationship of the drug level
between serum and tissue were analyzed by the use of the regression analysis, and the indirectly
predictive equation about the drag concentration in tissue is established.
The data were analyzed with the Pharma~olinetics computer program MCP-KP.
Phamiacolinetics show that the blood concentration-time course can be described with the first
compartment open model with the first order absorption alter oral administration( 10mg/kg) .Its
theoretical equation was as follows: CbI .036 (eI735t - e2057t), its main pharmacokinetics
parameters t1,.3.793his. t...I.5807brs.. c0.7429 i g/ml.. AUC5.3790 i g/ml. h0
The kinetics process Sarafloxacin Hydrochloride in tissues: the heart concentration -time
(C1-T) data of Sarafloxacin Hydrochloride was best described by a triexponential equation
with flint order absorption.Its theoretical equation was as follows: Ch = 0.1455e0 43+2.484&
OS44O3L2629e lS6I7t its main pharmacokinetics parameters t117.765hrs t111 .6027
tl.6826 hrs c0.5129 j.i g/ml . AUC9.0265 .t g/ml. h0
The heart concentration -time (C-T3 data of Sarafloxacin Hydrochloride was best
described by a triexponential equation with first order absorption.Its theoretical equation was as
-O.12&-02111t -04976t
follows: Ck = I .703e +0.3283e -2.031 2e , its main pharmacokinetics parameters
t1, 40.26 hrs.. t4.418hrs. t 1.9855 hrs c0.9090 i g/ml., AUC1O.894 .t g/ml. h
The liver concentration -time (C1-T3 data of Sarafloxacin Hydrochloride was best
described by a biexponential equation with first order absorption.Its theoretical equation was as
-018103t .O1IO&
follows: C1= 6.732(e - e ), its main pharmacokinetics parameters tl,2k3.1587hIS
t1,1.9764hrs. c3.737 j.t gin 1.. AUC31.354 5.1 giml. h.
The muscle concentration -time (C1-T1) data of Sarafloxacin Hydrochloride was best
described by a biexponential equation with first order absorption.Its theoretical equation was as
follows: Cm 0.91 88(e0157 - eO2OI4t) its main pharmacokinetics parameters t112k4. l24hrs-.
t,3.5679hrs.. c0.6956 ji giml.. AUC5.3269 g/ml. hrs.
Tissue phannacokinetics indicates Sarafloxacin Hydrochloride concentration in tissue is the
highest for liver, and lower for kidney and muscle, and the lowest for the heart. And the
residue time of drug in kidney is longer than that in the other tissue..According to the
elimination regularity of serum. heart liver., kidney and muscle,the time taken by the drag
concentration dropping to 0.OIug/ml is calculated.They were 5.58(hrs), 49.83(hrs),
32.63brs) ,160.02(hrs), 29.43(hrs).
The drug concentration in serum and tissue is analyzed by the use of the liner regression
equation in one unknow and multi-unkow, and the curvilinear regression equation in one
unkow. The results indicate that the dynamic variation regularity of the drug concentration in
serum and tissue can be better studied with this two analysis method, and the curvilinear
regression is better than the linear one in entirety and accuracy.The purpose of prediction the
drug concentration in tissue indirectly is achieved by the use of various regression equations.
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62、Martinsen B.et al. Single Dose Kinetic study of Sarafloxacin after Introvenous and Oral administration of different Formulations to Atlantic Salmon(Salmo Salar) held in sea Water at 8.5' C.Aquiculture. 1993.18:37-47.
63、Martinsen B.et al. Multiple-dose Pharmacolinetic and Depletion studies of Sarafloxacin in Atlantic Salmon(Salmo Salar):Journal of Fish Disease. 1994.17.111-121.
64、Martinsen B.et al. Comparative single-dose pharmacokinetics of four quinolones,Oxolinic acid,flumequine,salafloxacin and enrofloxacin in Atlantic Salmon held in sea water at 10 degree C. Antimicrob Agents Chemother. 1995.39(5): 1059-1064.
65、Hoshupeng et al. Pharmacokinetic and depletion studies of sarafloxacin after oral administration to ell.Journal of Veterinary Medical Science. 1999.61(5):459-463.
66、邱银生，盐酸沙拉沙星在鸡体内的药物代谢动力学研究，1998，待发表。
67、李银生，盐酸沙拉沙星在兔体内的药物代谢动力学及生物利用度的研究，1999，东北农业大学硕士学位论文。
68、Bauer J.F. et al..HPLC method for the simutaneous ditermination of enrofloxacin and its primary metabolite ciprofloxacin in caine serum and prestatic tissue. Joural of chromatography. 1987,80(1): 173-186.
69、Steffenak I.et al. A Rapid Assay for the determination of several Quinolones Antibacterials in medicated fish feed. Joural of chromatography. 1991.514.348-354.
70、Hormazabal V. et al. Rapid Assay for Monitoring Residues of enrofloxacin and sarafloxacin in Fish tissues by High Performance Liquid Chromatography. Journal of Liquid Chromatography. 1991.14(8): 1605-1614.
71、Meinertz J.R. et al. Liquid Chromatographic of sarafloxacin residues in channel Catfish muscle tissue. Journal of AOAC International. 1994.77(4):871-875.
72、Roybal J.E.et al. Determination of four Fluoroquinlones in milk by Liquid Chromatography. Journal of AOAC Lnternational. 1997.80(5):982-987.
73、Hormazahal et al. Journal of Liquid Chromatography. 1991.
74、Maxwell et al. Deternation of Sarafloxacin residues in fortified and incurred eggs on-line microdialysis and HPLC programmable fluorescence detection. Journal of Agricultural and Food Chemistry. 1999.47(4): 1563-1567.
75、邱银生，喳诺酮类在动物组织中的残留，中国兽药杂志，1996，30(1)：4749。
76、安登魁，药物分析，1996年，人民卫生出版社，第三版。
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79、悉念朱，药剂学，1997，人民卫生出版社，第三版。
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60、Stamme,J M et al,Effects of sarafloxacin hydrochloride on human enteric bacteria under simulated human gut conditions. Vet Q. 1995.17(1).
61、曾振灵，氟喹诺酮类抗菌剂在畜禽体内的药物动力学研究进展，中国兽药杂志，1994，28(4)。
62、Martinsen B.et al. Single Dose Kinetic study of Sarafloxacin after Introvenous and Oral administration of different Formulations to Atlantic Salmon(Salmo Salar) held in sea Water at 8.5' C.Aquiculture. 1993.18:37-47.
63、Martinsen B.et al. Multiple-dose Pharmacolinetic and Depletion studies of Sarafloxacin in Atlantic Salmon(Salmo Salar):Journal of Fish Disease. 1994.17.111-121.
64、Martinsen B.et al. Comparative single-dose pharmacokinetics of four quinolones,Oxolinic acid,flumequine,salafloxacin and enrofloxacin in Atlantic Salmon held in sea water at 10 degree C. Antimicrob Agents Chemother. 1995.39(5): 1059-1064.
65、Hoshupeng et al. Pharmacokinetic and depletion studies of sarafloxacin after oral administration to ell.Journal of Veterinary Medical Science. 1999.61(5):459-463.
66、邱银生，盐酸沙拉沙星在鸡体内的药物代谢动力学研究，1998，待发表。
67、李银生，盐酸沙拉沙星在兔体内的药物代谢动力学及生物利用度的研究，1999，东北农业大学硕士学位论文。
68、Bauer J.F. et al..HPLC method for the simutaneous ditermination of enrofloxacin and its primary metabolite ciprofloxacin in caine serum and prestatic tissue. Joural of chromatography. 1987,80(1): 173-186.
69、Steffenak I.et al. A Rapid Assay for the determination of several Quinolones Antibacterials in medicated fish feed. Joural of chromatography. 1991.514.348-354.
70、Hormazabal V. et al. Rapid Assay for Monitoring Residues of enrofloxacin and sarafloxacin in Fish tissues by High Performance Liquid Chromatography. Journal of Liquid Chromatography. 1991.14(8): 1605-1614.
71、Meinertz J.R. et al. Liquid Chromatographic of sarafloxacin residues in channel Catfish muscle tissue. Journal of AOAC International. 1994.77(4):871-875.
72、Roybal J.E.et al. Determination of four Fluoroquinlones in milk by Liquid Chromatography. Journal of AOAC Lnternational. 1997.80(5):982-987.
73、Hormazahal et al. Journal of Liquid Chromatography. 1991.
74、Maxwell et al. Deternation of Sarafloxacin residues in fortified and incurred eggs on-line microdialysis and HPLC programmable fluorescence detection. Journal of Agricultural and Food Chemistry. 1999.47(4): 1563-1567.
75、邱银生，喳诺酮类在动物组织中的残留，中国兽药杂志，1996，30(1)：4749。
76、安登魁，药物分析，1996年，人民卫生出版社，第三版。
77、南京药学院药物分析教研室，体内药物分析，1982，人民出版社。
78、李涛，药物代谢动力学原理，东北农学院内部教材，1982。
79、悉念朱，药剂学，1997，人民卫生出版社，第三版。