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测量伊曲康唑口服液血药浓度在血液科领域的临床意义。

Clinical significance of measuring the blood concentration of itraconazole oral solution in the field of hematology.

机构信息

Pharmaceutical Health Care and Sciences, Tokyo University of Pharmacy and Life Science, 1432–1 Horinouchi, Hachiouji, Tokyo 192–0392, Japan.

出版信息

Biol Pharm Bull. 2010;33(11):1861-6. doi: 10.1248/bpb.33.1861.

Abstract

Some studies indicated that preventive therapy with Itraconazole oral solution (ITCZ-OS) significantly decreased the incidence of invasive fungal infection, whereas others emphasized that there was no significant decrease. On the other hand, a study involving patients with neutropenia showed a 15-fold increase in the blood concentration of Itraconazole (ITCZ). Therefore, when administering ITCZ-OS, which is more rapidly absorbed in the digestive tract compared to its conventional dosage forms, to patients with blood disease, the blood concentration of ITCZ should be measured to maintain its efficacy and safety. To promote the appropriate use of ITCZ-OS, we conducted blood drug concentration monitoring, and investigated its clinical significance. The subjects were 26 patients with blood diseases. The blood level of ITCZ was measured using HPLC. The mean blood level of ITCZ was 2396.5±1742.7 ng/ml (mean±S.D.). The mean blood level of hydroxy-ITCZ was 5384.4±3348.2 ng/ml. The dose was not correlated with the blood levels of ITCZ/hydroxy-ITCZ per body weight (R(2)=0.134, 0.154, p=0.094, 0.071). Furthermore, the blood levels of ITCZ and hydroxy-ITCZ per body weight were significantly higher in females (p=0.025, 0.010). In males, there was a correlation between the creatinine clearance and blood level of ITCZ per body weight (R(2)=0.319, p=0.044). The blood levels of ITCZ varied among the patients. In addition, when ITCZ-OS was administered at a daily dose of 200 mg (ITCZ), the blood levels of ITCZ exceeded a trough level at which this agent may be effective in patients with febrile neutropenia in whom fungal infection is suspected.

摘要

一些研究表明,伊曲康唑口服液(ITCZ-OS)的预防性治疗可显著降低侵袭性真菌感染的发生率,而另一些研究则强调没有显著降低。另一方面,一项涉及中性粒细胞减少症患者的研究表明,伊曲康唑(ITCZ)的血药浓度增加了 15 倍。因此,在给血液病患者使用 ITCZ-OS 时,由于其在消化道中的吸收速度比常规剂型更快,应测量其血药浓度,以维持其疗效和安全性。为了促进 ITCZ-OS 的合理使用,我们进行了血药浓度监测,并探讨了其临床意义。研究对象为 26 例血液病患者。采用 HPLC 法测定 ITCZ 血药浓度。ITCZ 的平均血药浓度为 2396.5±1742.7ng/ml(平均值±标准差)。羟基-ITCZ 的平均血药浓度为 5384.4±3348.2ng/ml。剂量与 ITCZ/羟基-ITCZ 每体质量的血药浓度无相关性(R²=0.134,0.154,p=0.094,0.071)。此外,女性 ITCZ/羟基-ITCZ 每体质量的血药浓度明显高于男性(p=0.025,0.010)。在男性中,血肌酐清除率与 ITCZ 每体质量的血药浓度呈正相关(R²=0.319,p=0.044)。患者间 ITCZ 的血药浓度存在差异。此外,当以 200mg(ITCZ)的日剂量给予 ITCZ-OS 时,血药浓度超过了可能对疑似真菌感染的发热性中性粒细胞减少症患者有效的谷浓度。

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