In vitro activity of two phenyl-carbamate derivatives, singly and in combination with albendazole against albendazole-resistant Giardia intestinalis.
Giardia intestinalis is one of the most prevalent parasites in adults and children in Mexico. Benzimidazoles have been proposed as a therapeutic alternative in the treatment of giardiasis. However, high-dose related toxicity and the development of resistance have emerged in clinical trials using this therapy. In the search of alternative drugs, we found that benzimidazole-resistant strains of fungi have shown increased sensitivity to phenyl-carbamates, hence, we developed several substituted phenyl-carbamates, two of which were tested against the protozoan parasite G. intestinalis in susceptible and albendazole-resistant Giardia strains. 4-R-ethyl-phenyl-carbamates IRE-6A and IRE-7B demonstrated antigiardial, albeit modest, activity when compared with albendazole, against susceptible and albendazole-induced resistant Giardia. However, when albendazole 0.38 microg/mL (MIC(50)) was combined with each IRE compound, a significant antigiardial synergism (fractional inhibitory concentration index (FICI < 0.5)) was obtained not only with sensitive cultures but also with resistant Giardia parasites. The results described here suggest a potential role for a combined therapy with phenyl-carbamates and sub-doses of benzimidazoles in the treatment of giardiasis.
Jiménez-Cardoso
E
E
Hospital Infantil de México Federico Gómez, SS, Dr. Márquez #162, Col. Doctores, C.P. 06720 México, D.F., Mexico. enedina@servidor.unam.mx
Flores-Luna
A
A
Pérez-Urizar
J
J
D015766:Albendazole / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects; D004359:Drug Therapy, Combination; D016829:Giardia lamblia / Q000187:drug effects*; D015394:Molecular Structure
D000981:Antiprotozoal Agents; D002219:Carbamates; C481945:IRE-6A; C481946:IRE-7B; D015766:Albendazole