Comparison of plasma pharmacokinetic profile of ivermectin following administration of subcutaneous injection (Baymec®) and oral tablet (Efektin®) in goats

Abstract

The pharmacokinetic behaviour of ivermectin (IVM) has been investigated more extensively than that of the other members of the macrocyclic lactones, as IVM was the first avermectin used commercially and is the most widely used endectocide across animal species. IVM is available as oral, subcutaneous and topical formulations in the market to use in a wide variety of animal species. The pharmacokinetic behaviour of IVM is significantly affected by route of administration, formulation of the drug and interspecies variation (Lo et al., 1985). The previous studies showed that subcutaneous injection is a more efficient route for these drugs in terms of drug bioavailability in sheep, cattle and goats compared with oral and topical administration (Scott et al., 1990; Gayrard et al., 1999; Laffont et al., 2001; Lespine et al., 2003). In contrast to these observations, a recent study in dogs indicated that oral administration of IVM and doramectin injectable formulations displayed higher maximum plasma concentrations and similar persistence compared with subcutaneous administrations at the same dosage (Gokbulut et al., 2006a). This difference probably accounts for the different oral formulations of IVM as oral drench formulation was used in the previous studies, whereas injectable formulation administered in dogs. Hence, the differences in the oral formulations could affect the kinetic disposition of IVM. However, there is no available study on the comparative plasma disposition of oral tablet versus subcutaneous administration of IVM in goats. This study was designed to compare the plasma disposition of IVM in goats following oral (tablet) and subcutaneous administration at the same dosage. A total of 10 (four male and six female) cross-bred goats, 5–6 months old and weighing 18–26 kg, were used in the study. The animals were housed and fed twice with an appropriate quantity of feed during the experiment period. Water was supplied ad libitum. This study was approved by Animal Ethic Committee of University of Adnan Menderes. The animals were allocated into two groups of five such that the mean weight and sex of animals in each group was similar. Group I (IVM-SC) received subcutaneously the commercially available injectable solution of IVM (Baymec , 1% w/v, Bayer, Turkey) and group II (IVM-OR) received orally tablet formulation of IVM (Efektin , 10 mg/tablet, Sanovel, Turkey) at a dosage of 200 lg/kg bodyweight. Heparinized blood samples (5 mL) were collected 1 day prior to drug administration and 1, 2, 4, 8, 12, 16, 24, 32, 48, 72, 96 h and 6, 9, 12, 15, 20 25, 30, 35 and 40 days post-treatment. Blood samples were centrifuged at 2000 g for 20 min and plasma was transferred to plastic tubes. All the plasma samples were stored at )20 C until determination of drug concentration. The parent compound of IVM in plasma was analysed using validated high-performance liquid chromatography (HPLC) with a liquid–liquid phase extraction procedures. Plasma concentrations were measured by minor modification of the methods of Scott and McKellar (1992) and Gokbulut et al. (2001, 2005). A mobile phase consisting of acetonitrile and methanol (66:34 v/v) was delivered (Agilent 1100 Series QuatPump, Waldron, Germany) at a flow rate of 1.3 mL/min. A Nemesis nukleosil C18 column (4 l, 150 · 4.6 mm) (Phenomenex, Cheshire, UK) with nucleosil C18 guard column (Phenomenex) was used for an analysis of IVM. Fluorescence detection (Agilent 1100 Series, FLD Waldron, Germany) was at an excitation wavelength of 365 nm and an emission wavelength of 475 nm. The analytical method used for IVM in goat plasma was validated prior to the start of the studies. Calibration graphs for IVM were prepared (linear range 0.1–100 ng/mL). The slope of the lines between peak areas and drug concentration was determined by least squares linear regression and showed a correlation coefficient at 0.9994. The mean baseline noise at the peak retention time plus three standard deviations was defined as the detection limit (0.04 ng/mL). The mean baseline noise plus six standard deviations was defined as the limit of quantification. The limits of quantification of the assay were 0.15 ng/mL. The mean extraction recoveries were 80.9% (inter assay CV 3.46%). The plasma concentration vs. time curves obtained after each treatment in individual animals were fitted with the WinNonlin J. vet. Pharmacol. Therap. 30, 489–491, doi: 10.1111/j.1365-2885.2007.00888.x. SHORT COMMUNICATION