摘要
诺氟沙星是临床应用最广的一种喹诺酮类药物，多用其酸性制剂，随着诺氟沙星的应用，在临床已分离出许多对其耐药的菌株，这大大影响本药的治疗效果。我们在试验研究中发现，应用碱液配制的碱性诺氟沙星的治疗效果要好于酸性诺氟沙星
本文研究了酸性、碱性和长效诺氟沙星注射液的体外抑菌试验及其在健康猪体内的药动学试验。对8种细菌及7株耐药金葡菌的体外抑菌试验，结果显示：①、诺氟沙星对链球菌、变形杆菌、绿脓杆菌的作用相对较弱(MIC为4-8mg／L)，福氏痢疾杆菌、金葡菌对诺氟沙星敏感(MIC为0.03-0.25mg／L)，对产气荚膜杆菌的作用好于环丙沙星。②、对于标准菌株的抑菌作用，碱性诺氟沙星与长效诺氟沙星的体外抗菌作用相似。酸性诺氟沙星对链球菌的效果略优于碱性和长效诺氟沙星，对大肠杆菌、福氏痢疾杆菌的抗菌作用差异不显著。对金葡菌、沙门氏杆菌、变形杆菌、绿脓杆菌、产气荚膜杆菌的抗菌效果，碱性和长效诺氟沙星明显好于酸性诺氟沙星。③、对于耐药的金葡菌，各药的抗菌活性均减弱，标准菌株的MIC为0.125-0.25mg／L，MBC为0.25-4mg／L，而耐药菌株的MIC为2-64mg／L；MBC为4-64mg／L，其中YL2、YL7对酸性诺氟沙星的MIC、MBC值均大于64mg／L。④、碱性和长效诺氟沙星对耐药金葡菌的作用强于酸性诺氟沙星。对30头健康猪进行了三种制剂肌肉注射及静脉注射的体内药动学研究，应用HPLC法测定血药浓度，所得数据应用MCPKP药动学软件处理，结果为：①、肌注酸性诺氟沙星C_(max)3.50234±1.43539ug／ml，T_(1/2)4.28715±3.39786h，AUC14.031±3.859mg／l.h，F51.1％；②、肌注碱性诺氟沙星C_(max)2.63080±0.68306ug／ml，T_(1/2)6.07517±3.04761h，AUC12.499±2.423mg／l.h，F48.4％；③、肌注长效诺氟沙星C_(max)1.221397±0.05590ug／ml，T_(1/2)24.12160±7.75867h，AUC19.655±2.373mg／l.h，F76.3％；④静注酸性诺氟沙星Co13.84376±8.85363ug／ml，T_(1/2)3.29670±0.39538h，AUC27.477±2.007mg／l.h；⑤静注碱性诺氟沙星Co12.73648±5.18352ug／ml，T(1/2)3.31289±0.48439h，AUC25.747±3.149mg／l.h。
研究结果表明：(1)、碱性和长效诺氟沙星的抑菌效果相似，对多种细菌的抑菌效果好于酸性诺氟沙星，对耐药金葡菌的抗菌作用优势更为明显。(2)、静注酸性诺氟沙星和碱性诺氟沙星的药动学参数差异不显著。(3)、肌注的药动学参数差异显著，表明三种制剂在健康猪体内的吸收、分布和代谢是不同的。特别是长效制剂的消除半衰期延长4-8倍，可减少临床给药次数；生物利用度提高近30％，说明长效诺氟沙星肌注可大大提高药物在体内的浓度，增强药物疗效。
The Antibacterial Activity and Pharmacokinetics of acidic, alkaline and long effect norfloxacin injections were studied. The inhibitory activity experiment against seven drug resistant S.aureus and eight other bacteria were carried out .It resulted that the activity of three norfloxacin injections against Streptococcus, Bacillus protus and Pseudomonas aeruginosa is relatively inferior (MIC is 4-8mg/L), Shigella flexneri and S.aureus were susceptible (MIC were 0.03-0.25mg/L), the effect of norfloxacin was better than Ciprofloxacin against Cl. Perfringers. The comparative study of three norfloxacin injections reveals that the inhibitory effect of alkaline norfloxacin was similar to that of long effect norfloxacin, the acidic norfloxacin was a little better than alkaline or long effect norfloxacin against Sereptococcus in vitro. There was no difference between the activity of norfloxacin against E.coli and Shigella flexneri. The inhibitory activity of Alkaline and long effect norfloxacin injections against Stre
ptococcus, Salmonella, Bacillus protus and Pseudomonas aeruginosa were generally better than acidic norfloxacin. Compared with The standard stain (MIC 0.125-0.25mg/L), the results also indicated that the antibacterial activity of all of the three injections against drug resistant S.aureus were weak (>4000vg/ml). And against the two clinic isolated strains YLa and YLy, the MIC and MBC of acidic norfloxacin were more than 64mg/L, the alkaline and long effect norfloxacin were susceptible to drug resistant S.aureus than acidic norfloxacin, and they were susceptible to YL2 and YL7 than ciprofloxacin.
The pharmacokinetics of three norfloxacin injections were compared in healthy swines. Norfloxacin was given to health swines at a dosage of 10mg/kg of body weight im and iv in a complete crossover study. Norfloxacin concentration in plasma was assayed by a high performance liquid chromatograph (HPLC) method using an UV detector and the limit of detection of norfloxacin in plasma was 50ng/ml. All the data was processed by MCPKP computer software and the pharmacokinetics parameters were calculated, based on two-compartment open model. The results revealed that the parameters of acidic norfloxacin after single im dose: the maximal concentration (Cmax) was 3.50234 +1.43539ug/ml ;the elimination half life (T1/2,beta) was 4.28715 + 3.39786h; the area under curve (AUC) was 14.031 + 3.859mg/l.h, the bioavailability (F) was 51.1%, of alkaline norfloxacin after single im dose :the maximal concentration (Cmax) was 2.63080 +0.68306ug/ml, the elimination half life (T1/2,beta) was 6.07517+3.04761h, the area under curve (A
UC) was 12.499 + 2.423mg/l.h, the bioavailability (F) was 48.4%, of long effect
norfloxacin after single im dosing: the maximal concentration (Cmax) was 1.221397+0.05590ug/ml ;the elimination half life (Ti/2,beta) was 24.12160+ 7.75867h, the area under curve (AUC) was 19.655 + 2.373mg/l.h, the bioavailability (F) was 76.3%, of acidic norfloxacin after single iv dose: the Co was 13.84376 +8.85363ug/ml, the elimination half life (T1/2,beta) was 3.29670 +0.39538h, the area under curve (AUC) was 27.477 +2.007mg/l.h, of alkaline norfloxacin after single iv dose : the Co was 12.73648+5.18352ug/ml, the elimination half life (T1/2,beta) was 3.31289+0.48439h, the area under curve (AUC) was 25.747+3.149mg/l.h .
The results suggest that the inhibitory effect of alkaline norfloxacin was identical to that of long effect norfloxacin hi vitro and was better than that of acidic norfloxacin used against resistant S.aureus obviously. After evaluating all the parameters, there was no significant difference found between acidic and alkaline norfloxacin after single iv dose. There were significant difference found among acidic, alkaline and long effect norfloxacin after single im dose after statistical analysis (P less than 0.05), especially, the elimination half life of long effect norfloxacin could prolong four to eight times, improved bioavailability approximation 30%. From the above result, long effect norfloxacin could im
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