Studies On Metabolism And Toxicity Of Thiamphenicol In Cyprinus Carpio L.

The carp was used as laboratory animal to study the metabolic and toxicity ofThiamphenicol in the carp, the experiment used single-dose administration of TAP bymouth filling method to study the drug accumulation, and serum inhibitory effect,drugs metabolize law in tissues, the amount of drug accumulation, enzyme content ofthe active substance activity were measured; and blood cell morphology, quantity,physiological and biochemical indexes of serum, antioxidant function of liver andspleen, tissue damage were measured under high dose of TAP. The experimentstudied the pharmacokinetics of TAP in vivo, pharmacodynamics in vitro, the drugresidues, and toxic,aimed to provide a scientific theory basis for fair and standardizeduse during carp culturation.1. The drug use was30mg·kg-1with single dose by mouth filling method. Thepharmacodynamics result showed that Synchronous model parameter of PK-PD inserum AUC/MIC was35.37h, Cmax/MIC was24.89. Sigmoid Emax model ofinhibiting effect showed the optimal use dosage of TAP for the control of carpbacterial sepsis was47.94mg.kg-1.2. The drug use was30mg·kg-1with single dose by mouth filling method. The resultsof pharmacokinetic of TAP fited two-compartment open model with first-orderabsorption in the carp, the absorption and distribution of TAP was rapid,metabolismwas slow. The main pharmacokinetic parameters of TAP in the carpplasma, liver, kidney and muscle were as follows: elimination half-life (t1/2β) were77.292,24.625,79.966, and25.600h;distribution of half-life (t1/2α) were7.317,0.454,7.409, and1.376h; medicine area under the curve (AUC) were782.641,544.756,3616.060and158.634μg·g-1·h-1respectively.3. The drug use was recommended dose for3consecutive days. The result of drugresidues showed that the residues of TAP exist a downward trend.25d later theresidue was lower than the maximum residue limit50μg·mL-1of China and EU. Itwas proposed that the withdrawal time should be25days after administration. 4. The toxicity study TAP applied to carp: used1,3,5times the recommended doseby mouth filling method respectively. The result showed the number of fish bloodcells increased and decreased after a period of time, rate of micronucleus and nuclearanomalies increased with the dose increment; serum biochemical index TP, ALB, Cl,K, TBIL, ALT, AST, AKP, GLU, Na, Scr, TCH had significant difference in eachexperimental group, Ca increased significantly in3x group, UN reduced significantlyin1x and3x group; Liver, spleen antioxidant index determination showed that highdose of TAP could affect the normal physiological and biochemical function of theliver, spleen,mainly in the changes of CAT, SOD, MDA in liver and CAT, SOD, NOin spleen. Kidney, intestine, gill paraffin section observation showed theorganizational structure damaged aggravatingly with the dose increment.In the highdose group the tissue occurred cavitation, liver, spleen cells decreased,the nucleusdissolved;some amount of intestinal villus structure was not complete and fell off; gilltissue swelling occured.This showed that TAP was the common drug used to control disease infreshwater aquaculture, The results showed that in vitro efficacy of drugs onAeromonas hydrophila better inhibition; pharmacokinetic results showed thatitsabsorption and distribution was rapid, metabolismwas slow in the carp.pharmacodynamics in vitro result showed TAP had good effect to inhibitbacteria.While high dose of thiamphenicol affected the blood function and normalphysiological and biochemical indicators of liver and spleen, damaged the function ofliver, spleen, kidney, intestine, and gill. Thus, in the disease control periods, TAPshould be strictly used in accordance with the rules of scientific medicine,therecomended usage was47.94mg kg-1by mouth filling method for3or5days andthe withdrawal time should be25days after administration. Beware ofover-medication and prolonging drug treatment, in order to avoid damage to the carp.Kidney, spleen dysfunction carp, this drug should be used with caution; underlong-term high-dose, carp liver, kidney, and spleen were observed pathologicalchanges should immediately stop using it.