Wacke Rainer, Förster Sven, Adam Ulrich, Mundkowski Ralf G, Klar Ernst, Hopt Ulrich T, Drewelow Bernd
Institute of Clinical Pharmacology, Centre of Pharmacology and Toxicology, University of Rostock, Rostock, Germany.
J Antimicrob Chemother. 2006 Nov;58(5):994-9. doi: 10.1093/jac/dkl353. Epub 2006 Sep 6.
Failure to prevent secondary infectious complications in acute necrotizing pancreatitis (ANP) is attributable in part to the limited penetration of antimicrobial drugs. As newer quinolones are particularly attractive owing to their antimicrobial activity, for the first time we studied the penetration of moxifloxacin into pancreatic tissue in patients.
In this prospective, non-comparative clinical trial, 60 patients undergoing elective pancreas resection received a single oral or intravenous (iv) dose of 400 mg moxifloxacin for perioperative antimicrobial prophylaxis. The concentration of moxifloxacin was measured in samples taken from blood and from pancreatic tissue at the beginning and at the end of resection.
Mean moxifloxacin concentrations in pancreatic tissue following iv or oral administration were 3.1+/-0.9 and 2.7+/-1.4 mg/kg at 3-3.7 h post-dose (first sampling) and 3.6+/-1.5 and 3.1+/-1.8 mg/kg at 4.3-5.3 h post-dose (second sampling), respectively. Corresponding mean plasma concentrations of moxifloxacin were 1.8+/-0.5 and 1.2+/-0.6 mg/L (first sampling) and 1.5+/-0.4 and 1.0+/-0.5 mg/L (second sampling), respectively. From first to second sampling, the mean tissue-to-plasma ratios varied from 1.8+/-0.6 to 2.6+/-1.2 (iv) and from 2.4+/-0.8 to 3.1+/-1.2 (oral). Pancreatic tissue concentrations of moxifloxacin exceeded the MIC90 for the relevant pathogens covered by moxifloxacin for at least 5 h after dosing.
Moxifloxacin has been demonstrated to penetrate efficiently into human pancreatic tissue following iv or oral administration. From a pharmacological perspective, moxifloxacin appears to be promising for prophylaxis and treatment of local pancreas infections. Whether it is beneficial in the prevention and therapy of infectious complications in patients with ANP should be investigated in a controlled clinical trial.
急性坏死性胰腺炎（ANP）继发感染并发症预防失败部分归因于抗菌药物的穿透性有限。由于新型喹诺酮类药物具有抗菌活性，因而极具吸引力，我们首次对莫西沙星在患者胰腺组织中的穿透性进行了研究。
在这项前瞻性、非对照临床试验中，60例接受择期胰腺切除术的患者接受了单次口服或静脉注射400mg莫西沙星进行围手术期抗菌预防。在切除开始时和结束时采集血液和胰腺组织样本，测定其中莫西沙星的浓度。
静脉注射或口服给药后，给药后3 - 3.7小时（首次采样）胰腺组织中莫西沙星的平均浓度分别为3.1±0.9和2.7±1.4mg/kg，给药后4.3 - 5.3小时（第二次采样）分别为3.6±1.5和3.1±1.8mg/kg。相应的莫西沙星平均血浆浓度分别为1.8±0.5和1.2±0.6mg/L（首次采样）以及1.5±0.4和1.0±0.5mg/L（第二次采样）。从首次采样到第二次采样，平均组织与血浆浓度比在静脉注射组为1.8±0.6至2.6±1.2，口服组为2.4±0.8至3.1±1.2。给药后至少5小时，胰腺组织中莫西沙星的浓度超过了莫西沙星所覆盖相关病原体的MIC90。
已证明静脉注射或口服给药后，莫西沙星能有效穿透入人体胰腺组织。从药理学角度来看，莫西沙星在预防和治疗胰腺局部感染方面似乎很有前景。其在ANP患者感染并发症的预防和治疗中是否有益，应通过对照临床试验进行研究。
