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Teicoplanin is similar to Vancomycin and Norvancomycin which also belong to glycopeptide antibiotics, for the treatment of a variety of serious gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA) infections in clinical. A fat side chain is added on the chemical structure of teicoplanin, which results in increasion of its molecular weight and a good characteristics of the pharmacokinetics. Such as:a strong organization penetrating concentration in the cell and a significant longer elimination half-life. In addition to intravenous administration it can also be given intramuscularly. And It is reported that Teicoplanin against Staphylococcus aureus (SA) infections stronger than Vancomycin. The adverse reactions of Teicoplanin were generally mild and transient,so it is rarely discontinued in treatment, Besides serious adverse events are rare, the adverse reactions of Teicoplanin are also less than vancomycin,with aminoglycoside agents against renal damage are relatively minor.Teicoplanin has been used in the clinic, however, the literature which reports the treatment of endophthalmitis in the application is little.Because the exist of blood-ocular barrier, it is difficult to achieve effective drug concentration in the eye by intravenous and intramuscular injection. Therefore, local administration is often used in eye disease. Injecting the drug into the vitreous directly can well controll ocular inflammation, and a small dose is needed. Based on the above theory and teicoplanin own merits,this topice will investigate intraocular pharmacokinetic course and feature of teicoplan after rabbit eye intravitreous administration.And determinate the concentrations of teicoplanin in vitreous and aqueous humor. So it is can help to search a reasonable dose,for the treatment of ocular diseases in ophthalmology, compare the antibacterial activity against MRSA of teicoplanin with vancomycin, and Norvancomycin in vitro, which provides some theoretical basis for choosing reasonal drugs in the treatment of endophthalmitis especially in clinical.Methods33 young Japanese white rabbits were randomly divided into 11 groups of 3 rabbits.After Japanese white rabbits’right eyes injected teicoplanin 0.50mg/0.1ml to Vitreous body cavity,at 0,0.25,0.5,1,2,4,6,12,24,48,96,192h,extract vitreous and aqueous humor.The concentrations of teicoplanin were determined by bioassay,and the pharmacokinetic parameters were calculated by 3P97 pharmacokinetic software.We ueed two methods to determine the clinical MRSA isolates by K-B disk diffusion method and mecA gene detection by polymerase Chain reaction. To compare pharmacodynamic indices and minimal inhibitory concentrations for teicoplanin, vancomycin and Norvancomycin for methicillin-resistant Staphylococcus aureus isolates. Bacterial action of drugs with time as abscissa, to the strains at all time points the number of said colonies (mean±standard deviation) for the vertical axis, draw the time-killing curve.ResultsTeicoplanin standard calibration curve regression equation 1: y=0.174x-0.8131,R2=0.9991 (n=5), and it is a better linear relationship betwen 1.00 mg/L to 80.00mg/L. Teicoplanin standard calibration curve regression equation 2:y=0.1738x-0.804, R2= 0.9995 (n=5), and it is a better linear relationship betwen 100 mg/L to 350mg/L.The results show that it is in line with an open two-compartment model by a single intravitreal injection of teicoplanin.There is not absorption phase,but only the distribution and elimination phase in the vitreous. After Intravitreal injection of teicoplanin, and it is rapidly distributed in the vitreous, and gradually to aqueous dispersion of retinal and other organizations.At 15 minutes, the concentration of teicoplanin is 358.47±20.53mg/L,and at 192 hours is still 4.38±0.68mg/L. Teicoplanin have absorbed phase, phase distribution and elimination phase in the aqueous humor. Peak concentrations were 102.17±9.54mg/L, at 192 hours the concentration of Teicoplanin was 2.38±0.38mg/L.The pharmacokinetic parameters of Teicoplanin. The half-life of Teicoplanin in vitreous were 1.68h and 152.15h,AUC(O-t) was 259.94mg/L-h, AUC(O-∞) was 413.68mgL-h;CL was 0.001 L-h-1;K1-2 and K2-1 were 0.006min-1,0.373min-1.The half-life of Teicoplanin in aqueous were 2.83h and 70.56h;AUC(0-t) was 168.26mg/L-h, AUC(O-∞) was 245.049mg/L-h; CL was 0.002/L-h-1; rate constants K1-2 and K2-1 were 0.096min-1,1.409min-1The MIC and MBC values of teicoplanin were 0.5-lmg/L and 1.0-2.Omg/L; respectively vancomycin were 0.50-2.Omg/L and 1.0-4.0 mg/L,Nor-vancomycin 1-2mg/L and 8-16mg/L.The corresponding MIC50 and MIC90 values of teicoplanin were 0.49mg/Land 0.70mg/L,respectively vancomycin 0.62mg/L and 0.8mg/L;Nor-vancomycinl.25mg/L and 1.91mg/L.Teicoplanin,vancomycin,and Norvancomycin against MRSA in vitro.Different time points in the colonies, to do two factor analysis of variance. When the drug concentration was 100mg/L, at 10 hours bacteria colonies was zero, At this time the growth of all bacterial were inhibited,these three drugs on the antibacterial activity of MRSA were no significant difference. When the drug concentration was 10mg/L, at 10 hours teicoplanin, vancomycin groups of colonies were zero, MRSA growth was inhibited,but Norvancomycin aganst MRSA is weak, only partially inhibited, At this point teicoplanin, vancomycin against MRSA antibacterial activity was not significantly different, Teicoplanin, vancomycin and Norvancomycin against MRSA to antimicrobial activity were significantly different. When the drug concentration was lmg/L, the three kinds of antimicrobial drugs were only partially inhibited the growth of MRSA.Among the strongest inhibition teicoplanin, vancomycin, followed by the weakest Norvancomycin, this time, teicoplanin, vancomycin and Norvancomycin against MRSA to antimicrobial activity there significant difference. ConclusionAfter single intravitreal injection of teicoplanin 0.50mg/0.1ml, the line with two-compartment model. The drug treatment concentration Teicoplanin in vitreous, aqueous humor can maintained a longer time (about 192 hours).The t1/2αand t1/2βin vitreous were 1.68h,152.15h, and in aqueous were 2.83h,70.56h.In vitro,the MIC and MBC values of teicoplanin were lower than vancomycin, and Norvancomycin, antibacterial activity were significantly different.
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