02563nam a2200169 a 450000100080000000500110000800800410001910000160006024500960007626002500017252018480042265300280227065300200229865300270231865300190234570000290236415345972021-07-08       2008    bl uuuu     u01u1 u    #d1 aLANUSSE, C.  aModulation of cellular drug effluxbimpact on antiparasitic therapy.h[electronic resource]  aIn: CONGRESSO BRASILEIRO DE PARASITOLOGIA VETERINÁRIA, 15.; SEMINÁRIO DE PARASITOLOGIA VETERINÁRIA DOS PAÍSES DO MERCOSUL, 2., 2008, Curitiba. Programa e resumos. Curitiba: UFPR: Universidade Estadual de Londrina, 2008. 12 f. 1 CD-ROM.c2008  aThe progress achieved on the comprehension of the relationship among disposition kinetics, tissue distribution and the patterns of drug uptake/metabolism by different target parasites has greatly contributed to optimize parasite control in livestock. In vivo and in vitro studies have demonstrated that P-glicoprotein (P-gp) functions as an energy dependent efflux pump for many chemotherapeutic compounds, including some antiparasitic drugs. At the intestinal level, P-gp can actively transport a wide range of structurally diverse compounds out of the cell, pumping them back into the intestinal lumen. Therefore, P-gp may be involved both in limiting enteric absorption and facilitating intestinal secretion of different compounds, being an important determinant of drug systemic bioavailability. Different pharmacological approaches to delay the P-gp-mediated bile/intestinal secretions and to extend the plasma-intestine recycling time of the macrocyclic lactones (ivermectin, moxidectin) are currently being investigated. Their implications on the efficacy against resistant nematodes are under evaluation and some preliminary results are promissory.  On the other hand, some novel reported data reveal that a number of different P-gp´s are over-expressed in resistant Haemonchus contortus, and an enhanced drug efflux mechanism may be involved in the resistance of Fasciola hepatica to triclabendazole. Overall, the involvement of the efflux-transport protein P-gp (and perhaps other drug transporters) on both the pharmacokinetic disposition (host) and resistance mechanisms (target parasites) to different anthelmintic chemical groups, is described in the current article. Further work in the field is required to assess the practical pharmaco-parasitological implication of the chemical modulation of these cell efflux pump systems.  aantiparasitic compounds  acellular efflux  aDrug transport systems  aP-glycoprotein1 aBALLENT, M. LIFCHITZ, A.