Pharmacokinetics of abamectin in horses J. ECHEVERRI Â A N. MESTORINO E. TURIC J. PESOA & J. O. ERRECALDE* Ca Âtedra de Farmacologõ Âa, Farmacotecnia y Terape Âutica, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, cc 296 (1900), La Plata, Argentina. *Correspondence: E-mail: jerrecal@fcv.medvet.unlp.edu.ar; INCAM, VeroÂnica-Can ~uelas, 12 N°219 (1900), La Plata, Argentina. E-mail: jerrecal@yahoo.com (Paper received 13 February 2001; accepted for publication 16 May 2001) Abamectin (ABM) and ivermectin (IVM) are members of the macrocyclic lactone family known as avermectins (AVM) derived from Streptomyces avermitilis. Unlike IVM, ABM has a double bond at C22-C23. These highly lipophilic compounds have wide antiparasitic spectrum of activity (Fisher & Mrozik, 1992; Campbell, 1993). They are generally highly effective in control- ling gastrointestinal and lungworm larvae, adults and hypobiotic stages, but ineffective against ¯ukes and other ¯at worms (Marriner, 1986; Campbell, 1993). They are also very effective in controlling some ectoparasites. Abamectin reaches high concentrations in most tissues, especially in the liver and in the fat tissue (Campbell, 1993). In horses, a bimonthly treatment schedule with ABM during the period of risk has proved effective in helping to prevent adverse effects of the main target parasites, including large and small strongyles and stomach bots (Forbes, 1993). The target parasites in equine control programmes have different life cycles from those in cattle, many have longer migration periods, some of which progress in host tissues and so have longer prepatent periods. The activity of AVM, including ABM against early larval stages of many important parasites means that it can be given less frequently than other anthel- mintics. Because of problems caused by parenteral administration of IVM to horses (septic lesions at the injection site and clostridial myositis) in a low percentage of cases several years ago, the oral route has been favoured in this species (Pulliam & Preston, 1989; Anderson, 1984). It is well established that the ef®cacy of any anthelmintic drug depends on not only its af®nity for speci®c parasite target sites but also its ability to reach high and sustained drug concentra- tions where the parasites are located. Thus the value of pharmacokinetic studies in assessing anthelmintic drug ef®cacy depends on the assumption that the active concentration pro®le is similar at the site of action (Alvinerie et al., 1996). Therefore, understanding of the pharmacokinetic and metabolic patterns of the chosen drug can help to achieve optimal parasite control (Prichard et al., 1991). In this study, the pharmacokinetics of an oral ABM paste formulation in horses was examined. Six adult castrated male throughbred horses weighting 420±550 kg and kept on natural pasture were used. Commercial 10 g oral paste syringes containing 0.1 g ABM (Avotan gel Ò AG.003/97 series, Hoechst-Roussel Vet, Argentina) were used to administer 200 lg/kg to each horse. Horses were clinically normal with normal haemogram, liver enzymes and urine analysis. They were given mebendazole at a dosage of 25 mg/kg as antiparasitic agent 20 days before starting. Blood samples were taken in heparinized syringes at 0, 0.25, 0.5, 1, 2, 3, 6, 8, 10, 12, 15, 20, 25, 30, 35 and 40 days after treatment. Separated plasma samples were kept frozen at )20 °C until assayed by high performance liquid chromatography (HPLC) with ¯uorescence detection after solid phase extraction with C 18 cartridges (Alvinerie et al., 1987). The eluate was evaporated, derivatizated and injected into the HPLC system. A Shimadzu LC-10 AS (Shimodzu Corp., Kyoto, Japan) and a ¯uoromonitor TM III 1311 (LCD Analytical, Florida, USA) were used. The column was a C8 reverse phase Lichrospher and the mobile phase was glacial acetic acid:methanol:acetonitrile 9:200:csp 500 mL, at a ¯ow rate of 1.5 mL/min. The recovery rate was 80%. The limit of quanti®cation (lowest detected concentration resulting in coef®cient of variation lower than 20%) was 0.1 ng/mL. Variability was less than 8%. Pharmacokinetic analysis was performed through linear regression by using a program called Estrip (Brown & Manno, 1978). Mean ABM concentrations vs. time plots are presented in Fig. 1. Some pharmacokinetic parameters are presented in Table 1. With the tested ABM formulation, maximum plasma concentration (C max ) was lower and time of C max (T max ) longer than reported for IVM (76.3 ng/mL and 4 h: Marriner et al., 1987; 44 ng/mL and 9.2 h: Perez et al., 1999). Half life of absorption (T abs : 6.48 h) was longer than reported by Perez et al. (1999) for IVM (T abs : 01.57 h), but this is well correlated with the C max and T max . It should be noted that in the two IVM studies, sampling commenced earlier than 6 h post-treatment, however, the T max with ABM was ³ 24 h. Half-life of elimination J. vet. Pharmacol. Therap. 24, 359±360, 2001. SHORT COMMUNICATION Ó 2001 Blackwell Science Ltd 359