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


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 (t 1/2 = ?1.5 h), time to reach the maximum concentration (t max = ?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 ?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.

SUBMITTER: Schulz JD 

PROVIDER: S-EPMC6437472 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Schulz Jessica D JD   Neodo Anna A   Coulibaly Jean T JT   Keiser Jennifer J  

Antimicrobial agents and chemotherapy 20190327 4


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 albendazo  ...[more]

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