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阿苯达唑、阿苯达唑亚砜和阿苯达唑砜的药代动力学,通过感染钩虫的青少年的血浆、血液、干血斑和粪便样本进行测定。

Pharmacokinetics of Albendazole, Albendazole Sulfoxide, and Albendazole Sulfone Determined from Plasma, Blood, Dried-Blood Spots, and Mitra Samples of Hookworm-Infected Adolescents.

机构信息

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

University of Basel, Basel, Switzerland.

出版信息

Antimicrob Agents Chemother. 2019 Mar 27;63(4). doi: 10.1128/AAC.02489-18. Print 2019 Apr.

Abstract

Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population mostly affected by helminth infections. Blood microsampling would facilitate PK studies in pediatric populations but has not been applied to quantify albendazole's disposition. Quantification methods were developed and validated using liquid chromatography-tandem mass spectrometry to analyze albendazole and its metabolites albendazole sulfoxide and albendazole sulfone in wet samples (plasma and blood) and blood microsamples (dried-blood spots [DBS]; Mitra). The use of DBS was limited by a matrix effect and poor recovery, but the extraction efficiency was constant throughout the concentration range. Hookworm-infected adolescents were venous and capillary blood sampled posttreatment with 400 mg albendazole and 25 mg/kg oxantel pamoate. Similar half-life ( = ∼1.5 h), time to reach the maximum concentration ( = ∼2 h), and maximum concentration ( = 12.5 to 26.5 ng/ml) of albendazole were observed in the four matrices. The metabolites reached after ∼4 h with a of ca. 7 to 8 h. A statistically significant difference in albendazole sulfone's as determined by using DBS and wet samples was detected. of albendazole sulfoxide (288 to 380 ng/ml) did not differ among the matrices, but higher of albendazole sulfone were obtained in the two microsampling devices (22 ng/ml) versus the wet matrices (14 ng/ml). In conclusion, time-concentration profiles and PK results of the four matrices were similar, and the direct comparison of the two microsampling devices indicates that Mitra extraction was more robust during validation and can be recommended for future albendazole PK studies.

摘要

阿苯达唑是一种有效的驱虫药,已被广泛使用了几十年。然而,儿童(最易受到寄生虫感染的人群)的药代动力学(PK)特征尚未得到深入研究。血液微采样将有助于儿童人群的 PK 研究,但尚未应用于定量评估阿苯达唑的药物处置情况。我们开发并验证了液相色谱-串联质谱法,以定量分析湿样(血浆和血液)和血液微样本(干血斑 [DBS];Mitra)中的阿苯达唑及其代谢物阿苯达唑砜和阿苯达唑亚砜。DBS 的应用受到基质效应和回收率差的限制,但整个浓度范围内的提取效率是恒定的。在感染钩虫的青少年中,静脉和毛细血管血在接受 400mg 阿苯达唑和 25mg/kg 奥苯达唑后被取样。在四种基质中,阿苯达唑的半衰期(≈1.5 小时)、达到最大浓度的时间(≈2 小时)和最大浓度(12.5 至 26.5ng/ml)相似。代谢物在大约 4 小时后达到,清除半衰期约为 7 至 8 小时。使用 DBS 和湿样测定的阿苯达唑亚砜的达峰时间存在统计学差异。阿苯达唑亚砜的浓度(288 至 380ng/ml)在四种基质中没有差异,但在两种微采样设备(22ng/ml)中获得的阿苯达唑亚砜的浓度更高(22ng/ml)。在湿基质中(14ng/ml)。总之,四种基质的时间-浓度曲线和 PK 结果相似,两种微采样设备的直接比较表明,Mitra 提取在验证过程中更稳健,可推荐用于未来的阿苯达唑 PK 研究。

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