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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. and Neodo, Anna and Coulibaly, Jean T. and Keiser, Jennifer. (2019) Pharmacokinetics of albendazole, albendazole sulfoxide and albendazole sulfone determined from plasma, blood, dried blood spots and Mitra® samples of hookworm-infected adolescents. Antimicrobial agents and chemotherapy, 63 (4). e02489-18.

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Official URL: https://edoc.unibas.ch/70364/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Schulz, Jessica and Coulibaly, Jean and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Microbiology
ISSN:0066-4804
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:07 May 2019 07:20
Deposited On:07 May 2019 07:20

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