كتاب Comparative pharmacokinetics of ivermectin after its subcutaneous administration in healthy sheep and sheep infected with mange

Comparative pharmacokinetics of ivermectin after its subcutaneous administration in healthy sheep and sheep infected with mange من كتب طب بيطرى Comparative pharmacokinetics of ivermectin after its subcutaneous administration in healthy sheep and sheep infected with mange J. ECHEVERRI ́ A* , N. MESTORINO* , & J. O. ERRECALDE* , *Ca ́ tedra de Farmacologı ́ a, Farmacotecnia y Terape ́ utica, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina; INCAM, Vero ́ nica Experimental Station, La Plata, Argentina; (Paper received: 21 March 2001; accepted for publication 19 November 2001) Correspondence (e-mail: [email protected]) It is well established that the efficacy of any anthelmintic drug depends not only on its affinity for specific parasite target sites but also on its ability to reach high and sustained drug concentrations where the parasites are located. Ivermectin is one of the most useful anti-parasitic agents. It belongs to the family of avermectins that are highly lipophilic macrocyclic lactones. It is a fermentation product of Streptomyces avermitilis . One of the most important characteristics of iver- mectin is its wide spectrum of activity involving endo- and ectoparasites. Ivermectin is effective when it is applied orally, parenterally or topically. Its absorption is rapid by any of these routes of administration (Campbell, 1989, 1993). Mange is an ectoparasitic disease produced by the mite Psoroptes ovis . It has major economic importance in South America, especially Argentina, Chile and Uruguay. It is antici- pated that in the diseased animal there are kinetic modifications largely dependent on the change of body condition. The objective of the present paper was to determine the pharmacokinetic changes of ivermectin when applied subcutaneously to healthy animals and animals carrying natural mange infections. Six adult and healthy sheep (weighing 50 ± 6 kg) and five sheep naturally infested with psoroptic mites and showing mange lesions on at least 30% of their body surface (weighing 43 ± 6 kg) received 200 l g/kg ivermectin subcutaneously, the sampling times being at the following post-administration days: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 20, 25 and 30. Plasma was separated by centrifugation and kept frozen at ) 20 ° C until assayed. Assay was performed by high-performance liquid chromatography (HPLC). The recovery was 85% and the quantitation limit was 0.1 ng/mL. Variability was lower than 8%. The HPLC system was a Shimadzu LC-10 AS pump and TM III 1311 model fluoromonitor. The column was a C8 reverse phase lichrospher and the mobile phase was glacial acetic acid/ methanol/acetonitrile (9:200:291 mL) at a flow rate of 1.5 mL/ min. Reagents were HPLC grade. Extraction was accomplished by the solid–liquid method with C18 cartridges. The eluate was evaporated, derivatizated and injected into the HPLC system (Alvinerie et al ., 1987). Pharmacokinetic analysis wa
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