The Pharmacokinetics And Distribution Of Nitroimidazole Antimicrobials In Rat Oral Tissues

Nitroimidazole Antimicrobials are widely used for the treatment of anaerobic infections in dental clinic,the current dosage regimen is based on the pharmacokinetics of Nitroimidazole Antimicrobials in blood,it is still unclear about the distribution and pharmacokinetics of nitroimidazole antimicrobials in oral tissues,and it is also unclear whether the nitroimidazole antimicrobials could reach the effective concentration and achieve the maximum effect under current dosage regimen,so it is necessary to investigate the distribution and pharmacokinetics of nitroimidazole antimicrobials in oral tissues to provide necessary references for clinical drμg therapy.Rat was chosen as animal model in this research to investigate distribution of metronidazole,tinidazloe and ornidazole in gingiva,dental pulp, masseter muscle,and mandible by high performance liquid chromatography (HPLC)method.1.Pharmacokinetics and oral tissue distribution of metronidazole in ratsObjective:To develop appropriate HPLC method to measure the distribution of nitroimidazole antimicrobials in rat samples.Methods:for metrodizaole,the Agilent Zorbax SB-C18(250mm×4.6mm, 5μm)analytical columm was employed,the mobile phase consisted of watermethanol (70:30,v/v);and for tinidazole and ornidazole,the analytical columm was Agilent Zorbax SB- C18(150mm×4.6mm,5μm),the mobile phase consisted of water- methanol(75:25,v/v),20μl was pumped throμgh the system at a rat of 1.0ml/min, the effluent was monitored at 316 nm.The plasma and tissues homogenate sapmples of rats were extracted by 5%dimethylcarbinol chloroform,after centrifμgation the supematant were collected and dried for following analysis.Results:under the condition above,all chromatograms of metronidazole, tinidazole and ornidazole were free from any interference at the retention times, linear relationships were ranging from 31.25 to 12.5μ/ml with correlation coefficient above 0.999,and the limits of detection were 0.2ng with signal-to-noise ratio of 3.The mean recovery of metronidazole,tinidazole and ornidazole in rat tissues was 84.1%,86.2%and 85.4%respectively.The withinand between-day variability were all below 10%.Conclusion:A sensitive,accurate and rapid HPLC method was developed to quantitate concentration of nitroimidazole antimicrobials in rat oral tissues.2.The pharmacokineties and distribution of nitroimidazole antimierobiais in rat oral tissuesObjective:to observe and analyze the pharmacokinetics and distribution of metronidazole,tinidazole and ornidazole in rat gingival,dental pulp,masseter muscle and mandible.Methods:metronidazole and ornidazole 5mg/100g,tinidazole 4mg/ml was administered to male rats through intraperitoneal and tail vein injection.The samplaes of plasma,gingival,dental pulp and mandible were collected at different time interval.The pharmacokinetics of drug was analysed by established HPLC method.Results:1.Metronidazole,tinidazole and ornidazole could penetrate the oral tissues examined;2.The peak concentration of ornidazole in all the tissues was lower than metronidazole and ornidazole;3.The masseter muscle and mandible had the lowest drμg concentration among the tissues measured;4.In gingival and masseter muscle,the peak concentration of drμg in order was metronidazole＞tinidazole＞ornidazole,and in dental pulp and mandible that order was tinidazole＞metronidazole＞ornidazole;5.The peak-reaching time of ornidazole,which was 10 min in all the tissues, was shorter than other two drμgs,tinidazole reached the peak value at 30 min after drμg administration in all the tissues;metronidazole reached the peak value at 10 min after drμg administration in plasma and masseter muscle;30min in gingiva and 1h in dental pulp and mandible.6.The pharmacokinetics parameter of metronidazole and ornidazole was fit for one compartment model.Tinidazole was fit for two compartment model;7.Cmax value in order was metronidazole＞tinidazole＞ornidazole,eliminate half-time in order was metronidazole＞tinidazole＞ornidazole,total clearance in order was ornidazole＞metronidazole＞tinidazole;8.Tinidazole could maintain the effctive concentration in oral tissues for 8h, which was longest among three drμgs;ornidazole could only persist for 4.5h. Conclusions:all the three nitroimidazole antimicrobials could distributed in oral tissues,tinidazole is better relatively than metronidazole and ornidazole according to the overall parameter,which has more advatages for the treatment of anaerobic infections in oral tissues examined.