期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 63, 期 4, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02489-18
关键词
Mitra; albendazole; dried-blood spot; pharmacokinetics
资金
- Swiss National Science Foundation [320030_14930/1, 320030_175585]
- Swiss National Science Foundation (SNF) [320030_175585] Funding Source: Swiss National Science Foundation (SNF)
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 (t(1/2) = similar to 1.5 h), time to reach the maximum concentration (t(max) = similar to 2 h), and maximum concentration (C-max = 12.5 to 26.5 ng/ml) of albendazole were observed in the four matrices. The metabolites reached C-max after similar to 4 h with a t(1/2) of ca. 7 to 8 h. A statistically significant difference in albendazole sulfone's t(1/2) as determined by using DBS and wet samples was detected. C-max of albendazole sulfoxide (288 to 380 ng/ml) did not differ among the matrices, but higher C-max 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.
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