Gender-related differences on the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation. Journal of Pharmacy and Pharmacology

LIFSCHITZ, A; BALLENT, M; VIRKEL, G.; SALLOVITZ, J; LANUSSE, C

JOURNAL OF PHARMACY AND PHARMACOLOGY

PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN

Año: 2006 p. 1055 - 1062

0022-3573

Ivermectin (IVM), a macrocyclic lactone used as antiparasite agent, has been reported as a P-glycoprotein (P-gp) substrate. The possible participation of P-gp on the IVM excretion process was suggested. Sex-related differences on the kinetic behaviour of some macrocyclic lactone compounds have been observed. The aim of this work was to study the in vivo sex-related differences on the gastrointestinal disposition of ivermectin in the rat evaluating the involvement of P-gp and itraconazole (ITZ) modulation. Sixty (60) Wistar (30 male, 30 female) rats received IVM alone or co-administered with ITZ. Rats were sacrificed between 6 and 72 h post-treatment and blood, gastrointestinal tissues and lumen contents were collected. IVM concentrations were determined by HPLC. The co-administration with ITZ resulted in a marked increase of IVM concentrations in the wall tissue of different portions of the gastrointestinal tract of male rats. Substantial sex-related differences were observed on the IVM disposition kinetics. The ITZ-mediated modulation of the IVM disposition kinetics had a differential impact between male and female animals. The ITZ-mediated modulation of P-gp activity accounted for drastic changes on the IVM disposition kinetics, which resulted in marked differences dependent on the sex of the experimental animals.