title: Evaluation of albendazole prodrugs in experimental trichinellosis.
abstract: BACKGROUND
  Two albendazole (ABZ) prodrugs, N-methoxycarbonyl-N'-[(2-nitro-4-propylthio) phenyl] thiourea (compound 2), and N-methoxycarbonyl-N'-[(2-nitro-5-propylthio) phenyl] thiourea (compound 3) have recently been synthesized. These compounds showed greater solubility than ABZ itself.
  
  
  METHODS
  In order to evaluate the biotransformation of compounds 2 and 3 to ABZ and/or ABZ-sulphoxide (ABZ-SO), plasma samples taken from mice treated with the prodrugs were analyzed by HPLC. Also, the anthelmintic activity of compounds 2 and 3 against Trichinella spiralis was evaluated in the mice experimentally infected with the parasite.
  
  
  RESULTS
  The presence of ABZ and/or ABZ-SO was demonstrated in plasma samples taken at different time intervals after prodrug administration, although their levels were low compared to those reached in mice treated with ABZ. Additionally, prodrugs 2 and 3 were also detected in these samples. In regard to the anthelmintic activity of ABZ prodrugs, it was shown that compound 3 was more active than compound 2. Additionally, it was as effective as ABZ against T. spiralis pre-adult, adult, and female fecundity. However, compound 3 was not as active as ABZ against the muscle stage of the parasite.
  
  
  CONCLUSIONS
  Compound 3 had better anthelmintic activity against T. spiralis than compound 2. The bioconversion of compounds 2 and 3 to ABZ and/or ABZ-SO was demonstrated by HPLC, but they did not reach equivalent concentrations to that of ABZ. Prodrugs 2 and 3 were also present in plasma samples, suggesting that prodrugs were not efficiently reduced in the intestine of mice.
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Instituto Mexicano del Seguro Social, México, D.F., Mexico. lilianyepez@yahoo.com
authors.forename: L
authors.initials: L
authors.lastname: Yépez-Mulia
authors.forename: R
authors.initials: R
authors.lastname: Morales-Hurtado
authors.forename: N
authors.initials: N
authors.lastname: Viveros-Guzmán
authors.forename: R
authors.initials: R
authors.lastname: Cedillo-Rivera
authors.forename: F
authors.initials: F
authors.lastname: Hernández-Luis
authors.forename: R
authors.initials: R
authors.lastname: Castillo
authors.forename: A
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: O
authors.initials: O
authors.lastname: Muñoz
mesh_terms: D015766:Albendazole / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D014235:Trichinellosis / Q000188:drug therapy*
chemical_list: D000871:Anthelmintics; D015766:Albendazole