Membrane-water partitioning, membrane permeability, and baseline toxicity of the parasiticides ivermectin, albendazole, and morantel

Beate I. Escher, Cindy Berger, Nadine Bramaz, Jung-Hwan Kwon, Manuela Richter, Oksana Tsinman, Alex Avdeef

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A comparative hazard assessment of the antiparasitics ivermectin, albendazole, and morantel was performed, with a particular focus on bioavailability and uptake into biological membranes. The experimentally determined liposome-water distribution ratio at pH 7 (Dlipw (pH 7)) of the positively charged morantel was 100 L/kg lipid. The Dlipw (pH 7) of albendazole was 3,000 L/kg lipid. The membrane permeability determined with the parallel artificial membrane permeability assay was consistent with predictions from a quantitative structure-activity relationship (QSAR) for morantel but 14-fold lower than predicted for albendazole, which can be rationalized because neutral albendazole is, in fact, zwitterionic and the large dipole moment hinders permeation through hydrophobic membranes. An unusually large molecule, ivermectin was suspected to show decreased bioaccumulation because of its bulkiness, but experimental determination of solubility showed that it was 40-fold less soluble than expected from a QSAR between solubility and the octanol-water partition coefficient. In contrast, its membrane permeability appeared to be typical for a compound of the given hydrophobicity, but it was not possible to determine the membrane-water partition coefficient because of its low solubility and high affinity to the dialysis membrane of the experimental device. The Dlipw (pH 7) for ivermectin of 2,700 L/kg lipid was calculated with a QSAR model. Morantel and albendazole were baseline toxicants in the bioluminescence inhibition test with Vibrio fischeri and a test for inhibition of photosynthesis in green algae. Only ivermectin exhibited a specific effect toward algae, but the excess toxicity was not very pronounced and might be biased by the uncertainty of the estimated hydrophobicity descriptor. Overall, we did not find any unexpected effect on nontarget endpoints.

Original languageEnglish
Pages (from-to)909-918
Number of pages10
JournalEnvironmental Toxicology and Chemistry
Volume27
Issue number4
DOIs
Publication statusPublished - 2008 Apr 1
Externally publishedYes

Fingerprint

Morantel
ivermectin
Antiparasitic Agents
Albendazole
Ivermectin
Toxicity
Permeability
partitioning
permeability
membrane
toxicity
Membranes
Quantitative Structure-Activity Relationship
Water
Liposomes
Solubility
Hydrophobicity
Algae
Lipids
solubility

Keywords

  • Aquatic organism
  • Baseline toxicity
  • Environmental risk assessment
  • Quantitative structure-activity relationship
  • Veterinary pharmaceuticals

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Membrane-water partitioning, membrane permeability, and baseline toxicity of the parasiticides ivermectin, albendazole, and morantel. / Escher, Beate I.; Berger, Cindy; Bramaz, Nadine; Kwon, Jung-Hwan; Richter, Manuela; Tsinman, Oksana; Avdeef, Alex.

In: Environmental Toxicology and Chemistry, Vol. 27, No. 4, 01.04.2008, p. 909-918.

Research output: Contribution to journalArticle

Escher, Beate I. ; Berger, Cindy ; Bramaz, Nadine ; Kwon, Jung-Hwan ; Richter, Manuela ; Tsinman, Oksana ; Avdeef, Alex. / Membrane-water partitioning, membrane permeability, and baseline toxicity of the parasiticides ivermectin, albendazole, and morantel. In: Environmental Toxicology and Chemistry. 2008 ; Vol. 27, No. 4. pp. 909-918.
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