INVESTIGADORES
ALVAREZ Luis Ignacio
artículos
Título:
Integrated assessment of ivermectin pharmacokinetics,efficacy against resistant Haemonchus contortus andP-glycoprotein expression in lambs treated at threedifferent dosage levels
Autor/es:
LUIS ALVAREZ, GONZALO SUAREZ, LAURA CEBALLOS, LAURA MORENO,CANDELA CANTON, ADRIÁN LIFSCHITZ, LAURA MATÉ, MARIANA BALLENT,GUILLERMO VIRKEL, CARLOS LANUSSE
Revista:
VETERINARY PARASITOLOGY
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2015 vol. 210 p. 53 - 63
ISSN:
0304-4017
Resumen:
tThe main goals of the current work were: (a) to assess the ivermectin (IVM) systemicexposure and plasma disposition kinetics after its administration at the recommendeddose, x5 and x10 doses to lambs, (b) to compare the clinical efficacy of the same IVMdosages in lambs infected with an IVM-resistant isolate of Haemonchus contortus, and (c)to assess the expression of the transporter protein P-glycoprotein (P-gp) in H. contortusrecovered at 14 days after administration of the IVM dose regimens. There were two sep-arated trials where IVM was administered either subcutaneously (SC, Experiment I) orintraruminally (IR, Experiment II). Each experiment involved twenty-four (24) lambs arti-ficially infected with a highly resistant H. contortus isolate. Animals were allocated into 4groups (n = 6) and treated with IVM at either 0.2 (IVMx1), 1 (IVMx5) or 2 mg/kg (IVMx10).Plasma samples were collected up to 12 days post-treatment and analysed by HPLC. Anuntreated-control Group was included to assess the comparative anthelmintic efficacy ofthe different treatments. The level of expression of Pgp in H. contortus specimens obtainedfrom lambs both untreated and IR treated with the different IVM doses was quantified byreal time PCR. Parametric and non-parametric tests were used to compare the statisticalsignificance of the results (P < 0.05). After the SC treatment, the IVM plasma area under theconcentration?time curve (AUC0?LOQ) increased from 41.9 (IVMSCx1) up to 221 (IVMSCx5) and287 (IVMSCx10)ng.day/mL and after the IR treatment from 20.8 (IVMIRx1) up to 121 (IVMIRx5)and 323 (IVMIRx10)ng.day/mL. Dose-adjusted AUC0?LOQand Cmax were similar among doses,demonstrating dose proportionality for IVM after both SC and IR administration at the threedifferent doses. The efficacies against resistant H. contortus after the SC treatment were 42%(IVMSC1), 75% (IVMSCx5) and 75% (IVMSCx10). However, the IR IVM treatment reached clinicalefficacies ranging from 48% (IVMIRx1) up to 96% (IVMIRx5) and 98% (IVMIRx10). None of theIR IVM treatments increased the expression of P-gp in adult H. contortus at 14 days post-treatment compared to samples collected from the untreated control group.