奈替米星在阑尾炎症中的药动学及药效学的研究

 目的：了解阑尾炎患者静脉输注奈替米星后阑尾组织中药物处里及有效浓度。方法：术前随机给予急诊患者0.3g单剂童奈替米星输注，术中采集血清及阑尾组织标本用TDx浏定药物浓度，计算血清及组织PK和动态组织穿透比、通透指数(PI)及抑制系数(IQ，c〈sub〉max组织〈/sub〉/MIC)。结果：输注后奈替米星迅速进入阑尾组织(无t〈sub〉lag〈/sub〉，k〈sub〉a〈/sub〉=1.5788 h〈sup〉-1〈/sup〉)并维持较高浓度；组织中药物呈一级吸收一级消除二室开放模型，血清及组织t〈sub〉〈/sub〉分别为2.12 h和2.77 h(P>0.05)；其阑尾组织PI为0.396，对应阑尾炎症组织常见致病菌IQ值大多数达到或大于10。结论：奈替米星在阑尾炎症组织具较高浓度，其组织消除基本与血清平行；每日0.3 g单剂量30 min静脉输注可满足阑尾组织中治疗浓度。

Clinical PK and PD of netilmicin penetrated into tissue in patients with appendicitis

OBJECTIVE: To study the PK/PD of netilmicin penetrated into the tissue of appendicitis. METHODS: Blood and tissue samples were obtained in appendectomy during 0～10 hours following 0.3 g single dose by intravenous bolus.Netilmicin concentrations in serum and tissue were determined by using TDx.Their PK behavior were analyzed by using PCNONLIN program (SCI,v 4.2).Penetration index (PI) and inhibitory quotient (IQ) were calculated by AUC tissue/AUC serum and c_max/MIC ratios,respectively. RESULTS: The PK of netilmicin in tissue was compatible with a two compartment with 1 st order input,1 st order output and no lag time open model.The average dynamic penetration ratios at 0～2 h,2～4 h and 4～6 h were 0.52,0.46 and 0.41,respectively.t_1/2βof serum and tissues were 2.12 h and 2.77 h (P＞0.05),respectively.PI of netilmicin was 0.396,and IQ for different isolates from appendicitis were above 8 and 10,respectively. CONCLUSIONS: The results demonstrated that 0.3 g single bolus once daily may achieve optimal peak to MIC ratios and satisfy with the treatment of patients with appendicitis.