The pharmacokinetics of topical doramectin in llamas (Lama glama) and alpacas (Lama pacos).

There are many factors (i.e. renal physiology, hepatic metabolism, etc.) between species that could lead to modifications in the pharmacokinetics and thus possibly changes in the therapeutic interval of a compound (Short, 1994). The dosage regimens in New World camelids is often determined with little information regarding the pharmacokinetics or unique physiology in llamas and alpacas. Doramectin (Dectomax Pour-on, Pfizer Inc., New York, NY, USA) is an avermectin endectocide (Goudie et al., 1993) approved for topical use in cattle. Topical (pour-on) administration has the advantages of being easier to administer and lacks injection site lesions. The pharmacokinetic parameters of the topical doramectin in cattle after a single, 0.5 mg/kg administration were: t1/2 of 9.8 days, maximum plasma concentration (Cmax) of 12.2 ng/mL, time of Cmax (Tmax) of 4.3 days, mean residence time (MRT) of 12.8 days, and detectable plasma concentrations 40 days postadministration (Gayrard et al., 1999). The objective of this project was to determine the pharmacokinetics of a single, 0.5 mg/kg dose of topically administered doramectin in llamas and alpacas. This will assist with determining possible differences in topical doramectin pharmacokinetics between these two species of New World camelids. Seven llamas (Lama glama) and seven alpacas (Lama pacos) were obtained from commercial sources and had not been treated with an avermectin/ milbemycin within 30 days prior to the start of the study. The animals were housed outdoors with water and hay available ad libitum. The procedures described below were approved by the Kansas State University Animal Care and Use Committee. Complete blood counts and serum biochemical panels were carried out prior to drug administration. The animals were clipped along the dorsal midline; leaving approximately 0.6 cm fiber length on the animal from the withers to the ischium. All animals received doramectin at a dose of 500 lg/kg, which is the same dose approved in the US for topical treatment in cattle. Blood samples were collected via jugular venipuncture prior to dosing and at 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 17, 20, 25, 30, 35, and 40 days postdose. Blood samples (10 mL) were collected into evacuated tubes containing Li heparin and centrifuged to obtain plasma. Samples were analyzed using modifications of previously described methods (Stout et al., 1994; Nowakowski et al., 1995) via liquid chromatography/mass spectrometry. The assay was validated for plasma from both species. There were no species effects on recovery, precision, or accuracy. Recovery of doramectin was >96% across the range of the assay (0.25–20 ng/ mL). Intra-day precision was ±10% with an accuracy ±13% of intended values with inter-day precision of ±5.6% with an accuracy of ±8.9%. A daily assay run was rejected if more than two of the six QCs for a given standard curve were >15% of their intended value or if both QCs at a single concentration were >15% of their intended concentration, the run was reassayed with fresh extractions. The lower limit of quantitation for doramectin was 0.21 ng/mL. This was 15% below the lowest standard curve concentration. Pharmacokinetic parameters were determined for each animal using noncompartmental analysis (Gibaldi & Perrier, 1982; Riviere, 1999). Parameters calculated for plasma were: area under the plasma concentrations vs. time curve (AUC0–¥), area under the moment curve (AUMC0–¥), mean residence time (MRT) was calculated by use of the equation. Maximum plasma concentration (Cmax) and Tmax were read directly from the data. The rate constant (k) was determined from the slope of the plasma concentration curve that included at least the last four time points with quantifiable doramectin concentrations. The half-life (t1/2) was calculated using t1/21⁄40.693/k, but should be interpreted with caution as the value results from nonintravenous administration. The AUC and AUMC were calculated by use of trapezoidal rule with extrapolation to infinity. For statistical analysis, the nonparametric Kruskal–Wallis one-way J. vet. Pharmacol. Therap. 27, 187–189, 2004. SHORT COMMUNICATION