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 ϭ ϳ1.5 h), time to reach the maximum concentration (t max ϭ ϳ2 h), and maximum concentration (C max ϭ 12.5 to 26.5 ng/ml) of albendazole were observed in the four matrices. The metabolites reached C max after ϳ4 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, timeconcentration 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.

High-Fat Breakfast Increases Bioavailability of Albendazole Compared to Low-Fat Breakfast: Single-Dose Study in Healthy Subjects

“…In another study ( Schulz et al, 2019 ), ten hookworm-infected adolescents (from 15 to 20 years of age) were orally treated with 400 mg albendazole and 25 mg/kg oxantel pamoate. They received oily fish on bread as a standardized breakfast before treatment, but they got very low concentrations of albendazole in plasma (24.5 ng/ml) and albendazole sulfoxide (288 ng/ml), around 20% of the concentrations that we got after high-fat breakfast, which can limit the efficacy of treatment.…”

Quantification of albendazole in tablets of combined composition

“…The findings correlate with the results of the other scientists' studies [12][13][14], which also experimentally confirm the absence of the effect of praziquantel on the results of the analysis of albendazole in the composition of the tablet mass. The proposed conditions for the spectrophotometric study are identical to those presented in other scientific papers on the determination of albendazole in tablet dosage forms [15].…”

Efficacy and safety of moxidectin and albendazole compared to ivermectin and albendazole co-administration in adolescents infected with Trichuris trichiura: a randomized controlled trial protocol

“…Study participants will receive a local high-fat breakfast before treatment 21 . Since population PK parameters of all three study drugs are available [30][31][32] , a sparse sampling approach will be applied to describe the population-based PK profiles of the individual drugs upon mono-or co-administration. Additionally, potential interference between moxidectin or ivermectin and albendazole will be assessed.…”