华西地区头孢三嗪的药效学与药代动力学的研究

STUDIES ON THE PHARMACODYNAMIC AND PHARMACOKINETIC OF ROCIPHIN IN WEST CHINA

头孢三嗪(ROC)对革兰氏阳性与阴性菌包括对头孢噻吩等耐药株均有高效,对奇异变形杆菌的抗菌作用最强,MIC_(50)与MIC_(90)分别为0.006与0.012μg/ml.ROC,CTX对绿脓杆菌的MIC_(50)和MIC_(90)分别为1:4,1:1及2:8μg/ml.ROC分别与丁胺卡那霉素、庆大霉素及妥布霉素联合均有明显抗菌协同作用,FIC≤0.5者分别为82.61%,91.30%与65.22%.ROC对12株标准株与耐药的绿脓杆菌分离的酶均甚稳定,但不及CTZ.用3H—DAP参入细菌及形态学的观察研究显示ROC单用或与氨基甙类合用均能明显抑制细胞壁合成.在6名成人交叉进行1.0g,ROC肌注与静注,其药代动力学参数Cmax为142.65与321.17μg/ml,T1/2Ke为7.8h,T1/2α与T1/2β为0.46与7.46h,Vd为0.17与0.106L/Kg,Cl为0.54与0.56L/h;AUC为1867.65与1788.01μg.h/ml.尿排泄量24h内为32%与43%.

In vitro it has beenfound that ROC was a potent antibioticapainst gram postitive and gram negativebacteria, including various strains resistantto cefalothin, cefazolin and cefamandole.Against all enterbacteriaceae, ROC was themost active agent, the MIC_(50) andMIC_(90) was 0.006 and 0.012μg/ mlrespectivily. In vitro 60 strains P.aeruginosa susceptibility tests showed thatthe MIC_(50) MTC_(90) of ROC were similarto ceftazidime and cefotaxime (1 and 4,1and 1,2 and 8μg/ ml). ROC in combina-tion with amikacin, gentamicin andtobramycin against P. acruginosa all dem-onstrated synergistic activitics (FIC≤0.5)82.16%, 91 .30% and 65.22% respectively.ROC, cefotaxime and ceftazidime werevery stable to 11 standard β-lactamasesand 9 β-lactamases extracted fromceftazidime resistant strains or P. ae-ruginosa. The incorporation of radio activeDAP into E. coli K12 DP50 SUP F etc.were strongly inhibited by ROC. But ROCdid not influence the incorpotation of3H-leucine into the P. acruginosa.Mophorlogical studies demonstratedfilamentous cells formation were inducedby ROC even at low concentration, thedamage of cell wall with ribosome loss ap-peared at higherconcentration. ROC incombination with aminoglycosides alsoshowed synerigstic effects of mophorlogicalchanges. The pharmacokinetic study ofROC in 6 healthy adults with 1 g, adminis-tered IM or Ⅳ in a cross over design study.The pharmacokinetic parameters of IMand Ⅳ: Cmax 142.65 and 321 .17μg/ ml;T1 / 2Ke 7.82h, T1 / 2 α 0.46h, T1 / 2β7.46h; Vd 0.17 and 0. 106 L / Kg; C1 10.54and 0.56 L/h; AUC 1867.65 and1788.01μg / m1 respectively. The urinaryexcretion or ROC during 24 h after IM andⅣ were 32% and 43% respectively.