Pharmacokinetics of albendazole, albendazole sulfoxide and albendazole sulfone determined from plasma, blood, dried blood spots and Mitra(R) samples of hookworm-infected adolescents [Clinical Therapeutics]

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 micro-sampling would facilitate PK studies in pediatric populations but has not been applied to quantify albendazole's disposition. Quantification methods were developed and validated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze albendazole and its metabolites albendazole sulfoxide and albendazole sulfone in wet (plasma, blood) and micro blood (dried blood spots (DBS), Mitra®) samples. Only, 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 post-treatment 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 = 12.5–26.5 ng/mL) of albendazole were observed in the four matrices. The metabolites reached C_max after ~4 h with a t_1/2 of ~7–8 h. A statistically significant difference in albendazole sulfone's t_1/2 as determined by DBS and wet samples was detected. C_max of albendazole sulfoxide (288–380 ng/mL) did not differ among the matrices but higher C_max of albendazole sulfone were obtained in the two micro-sampling devices (22 ng/mL) vs. 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 micro-sampling devices indicates that Mitra® extraction was more robust during validation and can be recommended for future albendazole PK studies.

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