Truffot-Pernot C, Ji B, Grosset J
Service de Bacteriologie et Virologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Tubercle. 1991 Mar;72(1):57-64. doi: 10.1016/0041-3879(91)90025-n.
The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/l. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacterial agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T1/2) of pefloxacin was longer than that of ofloxacin, but the T1/2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1%, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose--600 mg daily--such a dosage may be only moderately effective against human tuberculosis.
氧氟沙星对结核分枝杆菌和偶发分枝杆菌90%菌株的最低抑菌浓度（MIC90）为2mg/L。这比培氟沙星低三个稀释度，且完全在人体可达到的药物浓度范围内。两种喹诺酮类药物的抗结核活性均与菌株对其他抗分枝杆菌药物的耐药性无关。鸟分枝杆菌-胞内分枝杆菌对这两种化合物均耐药，MIC90大于16mg/L。两种化合物的最大血清浓度（Cmax）均随剂量增加而成比例增加。培氟沙星的终末消除半衰期（T1/2）比氧氟沙星长，但两种化合物在小鼠体内的T1/2均比在人体中短得多。培氟沙星的浓度曲线下面积（AUC）是氧氟沙星的两倍。在小鼠中，每日剂量高达150mg/kg的培氟沙星对结核分枝杆菌感染无活性：就生存率而言，氧氟沙星经灌胃或按0.1%的浓度掺入小鼠饮食中时，对结核分枝杆菌感染的最低有效剂量为每日150mg/kg，但就菌落形成单位计数而言，每日150mg/kg的氧氟沙星仅表现出与每日100mg/kg乙胺丁醇相似的中度活性。氧氟沙星对结核分枝杆菌感染的治疗效果与剂量相关：每日经灌胃给予300mg/kg或在小鼠饮食中含0.4%时，其治疗效果比低剂量时好得多。由于每日给予150mg/kg氧氟沙星的小鼠的AUC接近临床耐受剂量（每日600mg）的人体的AUC，这样的剂量对人类结核病可能仅具有中等疗效。
