The effect of intestinal trichinellosis on oral bioavailability of albendazole in mice.
The effect of Trichinella spiralis infection on the pharmacokinetic profile of orally administered albendazol has been investigated in mice during the intestinal phase of the disease. Swiss CD-1 mice were orally infected with 300 +/- 50 muscle larvae of T. spiralis and then treated with albendazole (ABZ) formulated in hydroxy-propyl-beta-cyclodextrins at the dose of 10 mg/kg given orally on days 0, 5, 10 and 22 post-infection (p.i.). Blood samples were taken at 0.25, 0.5, 0.75, 1, 5, 6 and 24 h post-treatment (p.t.). Adult worm establishment as well as the histopathological alterations induced in the small intestine was assessed on days 0, 5, 10 and 22 p.i. The area under the blood concentrations to time curve (AUC) for ABZ sulphoxide was not significantly higher in infected mice than in control during the first step of intestinal infection (day 5 p.i.), whereas in the late step (day 10 p.i.), it was significantly lower. On day 22 p.i., the AUC showed similar values in both groups. The histopathological analysis showed a transient acute inflammatory reaction that varied from moderate to severe as the infection progressed from the early to the late intestinal stage. After intestinal infection, the inflammation was mild or absent with no signs of chronic effects. The histopathological studies correlated with the pharmacokinetics of ABZ and show that after transient inflammation induced by intestinal T. spiralis infection, the mucosa is restored to allow absorption of ABZ up to levels comparable to those observed in non-infected controls.
Rodríguez
Juan José García
JJ
Dpto. Parasitología, Universidad Complutense de Madrid, Spain.
de Prada
Inmaculada
I
Durán
Juan José Torrado
JJ
Fernández
Francisco Bolás
FB
D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000469:parasitology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D010949:Plasma / Q000737:chemistry; D017160:Trichinella spiralis / Q000302:isolation & purification; D014235:Trichinellosis / Q000188:drug therapy* / Q000473:pathology
D000871:Anthelmintics; D015766:Albendazole