PHARMACOKINETIC ASSESSMENT OF IVERMECTIN (3.15%) LONG-ACTING FORMULATIONS

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

Nueva Zelanda

Congreso; Congreso de la Asociación Mundial de Parasitología Veterinaria WAAVP; 2005

WAAVP

Ivermectin (IVM) is a broad-spectrum antiparasitic drug extensively used in veterinary medicine. The composition of the pharmaceutical preparation affects IVM absorption and its systemic availability. After the introduction of the first approved IVM formulation (propylene glycol/glycerol formal 60:40) used at 200 µg/kg, different pharmaceutical modifications have been assayed to extend IVM persistent endectocide activity. Recently, IVM 3.15% long-acting (IVM-LA) preparations to be administered at 630 µg/kg to cattle were introduced into the veterinary pharmaceutical market. The work reported here was designed to evaluate the comparative IVM absorption pattern and plasma concentration profiles obtained after subcutaneous administration of two IVM-LA preparations (3.15 %) and the classic IVM formulation (1%). Twenty eight (28) Holstein heifers (180-200 kg) were divided in four (4) experimental groups (n=7) and treated subcutaneously as follows: Group A: IVM 1% given at 200 µg/kg (Ivomec, Merial), Group B: IVM 1% (Ivomec, Merial) administered at  630 µg/kg, Group C: IVM-LA (A) (3.15 %, Ivomec Gold, Merial) injected at 630 µg/kg and Group D: IVM-LA (B) (3.15 %, Premium, Lab. Over SA) administered at 630 µg/kg . Blood samples were taken between 1 and 90 days post-treatment and IVM plasma concentrations were determined by HPLC with fluorescence detection. Large kinetic differences were observed among the experimental groups. There were no differences in the persistence of IVM plasma concentrations after the administration of IVM 1 % formulation at the two used dose levels (200 and 630 µg/kg). Higher peak plasma concentration (Cmax) and  shorter mean residence time (MRT) were obtained for IVM 1 % given at  630 µg/kg (Group B) compared to the treatments with both IVM-LA preparations. The IVM-LA (A) formulation showed a more extended absorption process than IVM-LA (B) preparation, which accounted for a longer persistence of detectable IVM plasma concentrations. These pharmacokinetic results demonstrate that increasing the dose rate (3-fold) is not sufficient to extend the persistence of IVM antiparasitic activity. Pharmaceutical design and the type/quality of the vehicles used to prepare long-acting formulations are relevant to obtain a differential persistent efficacy, which could be considered advantageous compared to that achieved when the traditional IVM 1% preparation is administered to cattle.