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Evaluation of Albendazole Prodrugs in Experimental Trichinellosis

1999; Elsevier BV; Volume: 30; Issue: 5 Linguagem: Inglês

10.1016/s0188-0128(99)00054-8

1873-5487

Lilián Yépez-Mulía, Raúl Morales-Hurtado, Noemı́ Viveros-Guzmán, Roberto Cedillo-Rivera, Francisco Hernández‐Luis, Rafael Castillo, Alicia Hernández–Campos, Onofre Muñoz,

Parasite Biology and Host Interactions

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. 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 mice experimentally infected with the parasite. 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. 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. 1999 IMSS. Published by Elsevier Science Inc.