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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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Pharmacokinetic and toxicological data of spirolides after oral and intraperitoneal administration

Paz Otero1, Amparo Alfonso, Paula Rodríguez

  • 1Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|November 22, 2011
PubMed

Insights

Spirolides, marine toxins from Alexandrium ostenfeldii, show high toxicity in mice, with rapid absorption and excretion. This research provides crucial data for regulating these cyclic imine toxins.

Area of Science:

  • Marine toxicology
  • Natural product chemistry
  • Pharmacokinetics

Background:

  • Spirolides are cyclic imine marine toxins produced by Alexandrium ostenfeldii.
  • Limited data exists on spirolide toxicity, absorption, and excretion, hindering regulatory efforts.

Purpose of the Study:

  • To characterize the symptoms and toxicity of spirolides administered intraperitoneally (i.p.) and orally in mice.
  • To compare the i.p. toxicity of 13-desmethyl spirolide C (13-desMeC), 13,19-didesMeC (13,19-didesMeC), and 20-methyl spirolide G (20-Me-G).
  • To investigate the absorption and excretion profiles of spirolides in mice.

Main Methods:

  • Intraperitoneal and oral administration of purified spirolides to mice.
  • Bioassays to determine LD(50) values for different spirolides.
  • Analysis of blood, urine, and feces using liquid chromatography-mass spectrometry tandem (LC-MS/MS).

Main Results:

  • 13-desMeC and 13,19-didesMeC exhibited high toxicity with LD(50) values of 27.9 μg/kg and 32.2 μg/kg, respectively.
  • 20-Me-G showed no mortality up to 63.5 μg/kg when administered i.p.
  • Spirolides were detected in mouse blood within 15 minutes and in urine after 1 hour post-administration.

Conclusions:

  • Spirolides demonstrate significant toxicity and rapid pharmacokinetic behavior in mice.
  • This study provides essential data for the toxicological assessment and regulation of spirolides, particularly within the European Union.

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