| The following reports were presented for the application study of high performance liquid chromatographic-indirect photomation determi- nation (HPLC-IPD) method on the field of pharmaceutical analysis including three separated parts. In the problem, aminoglycoside and streptomycete antibiotics without ultraviolet absorption in biological and preparation samples were directly determined because putting in a determined reagent-normal be called probe reagent, and this probe reagent is nicotinamide here. By the HPLC-IPD method, that tasks were studied, including separated analysis, pharmacokinetics in the rats and patients had different disease and treated by specially designated method, pharmacokinetics effect of other antibiotics, the relationship between serum drug concentration and the kidney function change with different administration. And a few new viewpoints and results about HPLC-IPD method and aminoglycoside and streptomycete antibiotics were reported.Part One Establishing of HPLC-IPD methodsObjective : To established HPLC-IPD methods for determination of aminoglycoside and streptomycete antibiotics. Methods : In the light of fundamentals of HPLC and IPD, the chromatographic conditions and the simple disposal methods were optimum seeked. Netimicin, amikacin, gentamicin, sisomicin, tobramycin, lincomycin and clindamycin in the biological and preparation samples were determined. The biological samples were includingserum, plasma, urine, saliva, phlegm, cerebrospinal fluid, fluid oozed out from wound, bile, stool, viscera and tissue. Results and Conclustion: The HPLC-IPD methods established can be applied to determine aminoglycoside and streptomycete antibiotics in biological samples in Therapeutic Drug Monitoring (TDM).Part Two Applying of HPLC-IPD method in TDMChapter one Pharmacokinetics of netilmicin sulfateObjective: To investigate the pharmacokinetic of netilmicin sulfatein rats and patients. Methods.- After taking the drugs, the concentrations in the tissue and body fluids were determined by HPLC-IPD method and the datas of pharmacokinetic was conformed. Results and Conclustion: In rats, the dispostion of netilmicin was conformed to a single coppartment model in serum and there was a highest drug accumulation in liver, lung and kidney with a lowest in fat and brain. Drug excreted in urine, feces and bilewithin 24h was 74.4%, 1.70% and 4.84%. The pharmacokinetic in old patients contracted respiratory system infection was conformed to a dubble compartment model with t]/2 3.65h at intramuscular. There was a slight accumlation at repeated. The concentration of drug in phlegm had no correlation with in serum. The pharmacokinetic in the patients with impaired renal function was conformed to a dubble compartment model with tj/2 5.8+ 1.4h. After intravenous administration of netilmicin 5mg/kg, the peak concentration in serum of the patients with intestines fistula under total parenteral nutrition(TPN) were lower than the control (P<0.05) , but it in serum was higher than control(P>0.05) at 5h and significantly higher (P<0.05) at 12h after administration. The bioavail- lability of netilmicin was raised and reclamation in urine descended with cephradine.Chapter two Distribution of aminoglycoside and streptomycete antibiotics in nucleus of intervertebral discsObjective: To screeninged the antibiotics for nucleus infection thoughestablished the distribution of aminoglycoside and streptomycete antibiotics in nucleus of intervertebral discs in rabbit and patients. Methods: At 0.5 and lh after intravenous injection, the concentrations of the drugs in serum and in nucleus of intervertebral discs determined by HPLC-IPD methods. Results : The concentration ratio of nucleus to serum of rabbit were increased infected in nucleus than normal and this ratio of clindamycin is higher than tobramycin markedly (P<0.05) . The rates of removing on the antibiotics from nucleus were lower than from serum. The results in patients indicated that the quantities of antibiotics distributed to nucleus were significantly different and the quantities were not interrelated with the concentrations in serum. For different individuals, the amount of drug distributed to nucleus had significant differences. Conclusion: There is no interelation of the concentrations in nucleus and serum. Clindamycin, tobramycin and lincomycin are that antibiotics for treating infected intervertebral discs.Chapter three The kidney change for aminoglycoside antibiotics with different administrationObjective: To study the relationship between the kidney function change and the concentratios of gentamicin, amikacin and netimicin in serum with different administration. Methods: 62 patients were taken three drugs,and the therapeutic drug's concentrations were monitored by HPLC-IPD method. The kidney function was also nonitored. Results: The results showed the serum drug's concentration peak value was marked lower in divided two times than one time im & iv gtt for fives days (P<0.01) and the valley value was opposite to peak. Kidney function, Cr and BUN had almost no change in divided one time but had marked rised in divided two times. Conclusion: The result indicated that divided one time administration may raise the drug concentration in serum and reduce the nephrotoxic actions of aminoglycoside antibiotics.
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