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伊曲康唑间歇冲击疗法及其甲的药代动力学研究

PHARMACOKINETIC STUDY OF ITRACONAZOLE INTERMITTENT PULSE THERAPY IN TREATMENT OF ONYCHOMYCOSIS

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【作者】 宋守荣陈琼李若瑜王端礼崔一民

【Author】 SONG Shou-Rong*, CHEN Qiong, LI Ruo-Yu, WANG Duan-Li ,CUI Yi-Min** (Department of Dermatology and Pharmacology**, The First Hospital of Beijing Medical University, Beijing, 100034)

【机构】 北京医科大学第一附属医院皮肤科

【摘要】 本文采用不同剂量伊曲康唑间歇冲击疗法治疗22例甲真菌病患者,并用高压液相色谱法(HPLC)测定了伊曲康唑在甲板中的浓度。结果表明:400,300,200mg·d-1三个不同剂量组,服药后1周即可在指、趾甲远端测出药物,停药后6个月仍可在甲板中测到高于MIC的浓度。证明药物进入甲板有两条途径:一是通过甲床迅速弥散;二是与甲母细胞结合后进入。药物进入指甲的速度较进入趾甲为快,甲板中药物的浓度与口服药物的剂量呈正相关,400mg组明显高于200mg组。

【Abstract】 Twenty-two patients with onychomycosis were treated with Itraconazole intermittent pulse therapy dosed 200mg, 300mg and 400mg either for 2 or 3 cycles. The distal nail clippings were taken before initiation of therapy and 0.25,1,2,3,4,5,6,7,8,9(toenail only) months there after. The concentration of itraconazole in the nail plates were measured by HPLC assay. Therapeutic concentration of itraconazole can be detected in different dosage groups both in fingernail and toenail plates in the first week after the onset of treatment. Itraconazole could be detected in the nail until 6 months after the end of treatment. The data suggest that the drug reaches the nail via incorporation into the matrix and by diffusion from the nail bed and is eliminated with regrowth of the nail after discontinuation of treatment. The drug concentration measured at all time points are well above the MICs for dermatophytes and other fungi . These data show that itraconazole reaches the nail plate rapidly and persists there for longer time after the stop of treatment. The concentration of itraconazole in nail plate is related to the drug dose.

【关键词】 伊曲康唑甲真菌病药代动力学
【Key words】 itraconazoleonychomycosispharmacokinetics
  • 【文献出处】 中国临床药理学杂志 ,THE CHINESE JOURNAL OF CLINICAL PHARMACOLOGY , 编辑部邮箱 ,1998年02期
  • 【分类号】R978.5,R969.1
  • 【被引频次】3
  • 【下载频次】70
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