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

Antimicrob Agents Chemother. 2019 Mar 27;63(4):e02489-18. doi: 10.1128/AAC.02489-18. Print 2019 Apr.

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.

Keywords: Mitra; albendazole; dried-blood spot; pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Albendazole / analogs & derivatives*
  • Albendazole / blood
  • Albendazole / pharmacokinetics*
  • Albendazole / therapeutic use
  • Ancylostomatoidea / drug effects
  • Animals
  • Anthelmintics / blood
  • Anthelmintics / pharmacokinetics*
  • Anthelmintics / therapeutic use
  • Chromatography, Liquid / methods
  • Dried Blood Spot Testing / methods
  • Hookworm Infections / blood*
  • Hookworm Infections / drug therapy
  • Hookworm Infections / parasitology
  • Humans
  • Male
  • Plasma / chemistry*
  • Pyrantel Pamoate / analogs & derivatives
  • Pyrantel Pamoate / pharmacokinetics
  • Pyrantel Pamoate / therapeutic use
  • Tandem Mass Spectrometry / methods

Substances

  • Anthelmintics
  • albendazole sulfone
  • Pyrantel Pamoate
  • Albendazole
  • albendazole sulfoxide
  • oxantel pamoate