Study On The Pharmacokinetics In Pigs And Antibacterial Quantitative Structure-Activity Relationship Of Pyroline

Pyroline attached to hydroquinones is a novel antibacterial animal medicine. Its characters are wide antibacterial ranges strong action low toxicity no residual .~ not easy Produced antidrug effect and so on. Pyroline effect is of great significance when it is applied to cure cow mastitis.. porcine water fats porcine erysipelas and husbandry animal chylopoietic disease by many pathogenic bacteria in veterinary clinical practice. One hand, the experiment was to study the pharmacokinetics of pyroline in pigs in order to provide the theoretical basis for rational pharmacotherapy~ new animal medicine research and formulation improvement. On the other hand, the experiment was to study antibacterial quantitative structureactivity relationship of pyroline in order to pick out new bacterial animal medicine better than pyroline and to improve Chinese situation that animal medicines are short of many types and often dependent on man ones.1 . Five normal pigs were given pyroline iv 30mg kg?and im 85mg kg? The concentrations of pyroline in porcine plasma were determined with RP-HPLC method developed in our laboratory. A waters model 480 instrument was used throughout the experiment. Vanillin was used as the internal standard at absorption wavelength of38220nm.A mixture of methanol and water(40:60) was used as the mobile phase with aflow rate of 0.7ml. min-',and YWG-C., as stationary phase. Plasma drugconcentration-time course of pyroline aIier iv and im administration of pyroline wereboth tbulld to be fitted to two col11partmel1t opel1 1nodel and their pharmacokineticalwt ase wty as tbIlowrf iv, T. (. =l.52 nd. tl =66.05min,AUC=880.07mg. min. L-'; il11, T,;,.,,=0.37min, T.,, (. =3.45min, T,,, t) =76.87min,AUC=570. l7mg,1lin t-', Tp=l .53n1i11, Cn1ax=l l .34 ll g,nl-'. The results reveal thatPyrolille was absorbed rapidly. distribtlted wide. eliminated fast and its biovailabilitywas low. Combined with clinic cases, it was followed that pyroline effect was carriedout by such many mechanisms as antibiotic effect prolonged.2.Pyroline was acted as a lead compound and new fourteen compounds weresynthesized. After antibacterial effects were measured, hydroquine was acted asmother structure to study QSAR. Con1bined with clinic practice, staphylococcus wasselected as a pathogenic bacterium by which et1bctive coefficients were measured. Ittbllowed' QSAR equation was lgl/MIC=0.0350 rr -0.0l53 rr 2+0. l784 o +0.0020MR-l .62l3l+4.44l5 n=l3 r=0.8089 F=2.65(u =0.05),When iso-propylhydroquinonewere used to prove the equatiol1,tl1erc werc solne certain effective significance fOr itsequatiol1 tbrecasting compotll1d's activity. Tl1rough selecting significant actionpara111cters, it was tbllowed that tl1ere was 58% correlation between order variance (I)al1d antibacterial activity. TherefOr, al1tibacterial mechanism of hydroquinones wascarried out by oxidization and reduction reaction. The experiment provided somecertain clue and basis fOr finding thrther etTective pyrolines and explaining its actionmechanism.Study on the pharmacokinetics in pigs of pyroline has never reported in the world.AIthough research on QSAR of hydroquinones has ever reported by forefather, theexperiment finished QSAR first with order variance (I) and accordingly producedaction lnechanism.