title: Enantiomerical pharmacokinetic prevalence of (+) albendazole sulphoxide in Trichinella spiralis muscle larvae.
abstract: In a previous work, it was demonstrated that (+) albendazole sulphoxide (SOABZ) has higher anthelmintic activity than (-) SOABZ (Bolás-Fernández et al. J Parasitol 90:407-409, 2004). In this work, the pharmacokinetics characteristics of SOABZ and its enantiomeric forms were studied in an ex vivo model system for Trichinella spiralis isolated muscle larvae. To this end, samples of either racemic or purified SOABZ enantiomers were added to the incubation medium. Quantification of either albendazole, racemic SOABZ or its enantiomers was performed by validated HPLC methods and the effect of different SOABZ concentrations in relation to time of contact with the larvae was also analysed. Obviously, higher concentration of SOABZ in the medium leads to higher concentrations of SOABZ inside the larvae which increased in an exponential mode, thus indicating a simple diffusion process. At least 18 h of contact with the drug was required to achieve anthelmintic effects. Besides, after this time, the concentration of (+) SOABZ inside the larvae was significantly higher than that of the (-) SOABZ. From these results, it can be concluded that the higher activity found in the previous work is clearly related to the pharmacokinetic prevalence of (+) enantiomer inside the larvae.
authors.affiliation: Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal, s/n, 28040 Madrid, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: García-Rodríguez
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Del Vegas-Sánchez
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Torrado-Durán
authors.forename: Francisco
authors.initials: F
authors.lastname: Bolás-Fernández
mesh_terms: D015766:Albendazole / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000469:parasitology*; D013237:Stereoisomerism; D013997:Time Factors; D017160:Trichinella spiralis / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000871:Anthelmintics; D015766:Albendazole