Pharmacokinetic disposition and faecal excretion of pyrantel embonate following oral administration in horses C. GOKBULUT* , à A. M. NOLAN* & Q. A. MCKELLAR   *Division of Veterinary Pharmacology, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, UK;   Moredun Research Institute, Pentlands Science Park, Penicuik, Edinburgh, UK. à Correspondence (E-mail: 9602174g@udcf.gla.ac.uk) (Paper received 11 April 2000; accepted for publication 25 October 2000) Pyrantel (PYR) is an imidazothiazole derivative, which belongs to the tetrahydropyrimidine class of anthelmintics. It is available as tartrate and pamoate (syn. embonate) salts. Different salts of PYR have different pharmacokinetic properties and consequently different toxicities to the host. The pamoate salt is almost insoluble in water and poorly absorbed from the gastrointestinal tract and most passes unchanged in the faeces (Arundel, 1983). Reduced systemic absorption of the pamoate form potentially increases availability in the lumen of the intestine (Bjorn et al., 1996). The tartrate salt of PYR is soluble in water and absorbed rapidly and extensively from the intestine of monogastric animals (Faulkner et al., 1972). Pyrantel is highly effective (95±97%) against small strongyles, Parascaris equorum and Strongylus vulgaris, and has moderate activity against Strongylus edentatus (70%) and Oxyuris equi (65%) (Mirck, 1985). Continuous (30 days) low-level daily administration of PYR tartrate (2.65 mg/kg) to horses was highly effective against common gastrointestinal parasitic infec- tions of horses, including large strongyles (S. vulgaris, S. edentatus and Triodontophorus spp.), adult small strongyles (Cyathostomum spp., Cylicocyclus spp., and Cylicostephanus spp.), and adult and fourth-stage P. equorum (Valdez et al., 1995). There is a paucity of data available in the literature on the pharmacokinetics of PYR in horses. In the present study, the pharmacokinetic disposition and faecal excretion of PYR embonate are reported in horses after oral administration. Eight thoroughbred gelding horses weighing 525±570 kg were used in this study. Animals were kept at pasture during the experimental period. Horses were identi®ed by unique freeze brand or natural markings. A commercially available equine formulation of PYR embonate (Strongid-P, 43.9%, P®zer Ltd, Kent, UK) was administered orally as a single bolus dose at 13.3 mg/kg bodyweight to each animal. Heparinized blood samples were collected by jugular venipuncture prior to drug administration and at 1, 2, 4, 8, 12, 20, 24, 32, 48, 72, 96 and 120 h thereafter. Faecal samples (> 10 g) were also collected per rectum (p.r.) throughout the blood sampling period, before drug administration and then 4, 8, 12, 20, 24, 32, 48, 72, 96 and 120 h later in order to determine the faecal excretion. The samples were taken under Home Of®ce Regulations (Animal Scienti®c Procedure Act, 1986). Blood samples were centrifuged at 1825 g for 30 min and the recovered plasma was transferred to plastic-stoppered tubes. All plasma and faeces samples were stored at ±20 °C until estimation of drug concentration. The parent compound of PYR was analysed by high perform- ance liquid chromatography (HPLC). The liquid phase extraction procedure used for PYR was adapted from that described by McKellar et al. (1993). Brie¯y, 1 mL drug-free plasma samples were forti®ed with PYR standard to reach the following ®nal concentrations: 0.005, 0.01, 0.05, 0.1 and 0.5 lg/mL. Morantel citrate was used as an internal standard. Sodium hydroxide (NaOH) (0.5 mL, 0.4 M) was added to tubes. After vortexing for 15 sec, 6 mL chloroform were added. The tubes were shaken for 2 min. After centrifugation at 1825 g for 15 min, 4 mL of the organic phase were transferred to a glass tube and evaporated to dryness at 43 °C in a sample concentrator. The dry residue was dissolved in 300 lL of mobile phase and 100 lL of this solution was injected into the chromatographic system. Wet faecal material (10±100 g) was mixed with a spatula to obtain a homogeneous sample. Drug-free wet faecal samples (0.5 g) were forti®ed with PYR standard to reach the following ®nal concentrations: 0.5, 5, 50, 100 and 400 lg/g. Acetonitrile (2 mL) was added to tubes containing 0.5 g forti®ed blank samples and experimental samples. After vortexing for 15 sec, 6 mL chloroform were added. The tubes were shaken for 2 min. After centrifugation at 1825 g for 15 min, 4 mL of the organic phase were transferred to a glass tube and evaporated to dryness at 43 °C in the sample concentrator. The dry residue was dissolved in 300 lL of mobile phase and 50 lL of this solution was injected into the chromatographic system. Because of the photosensitivity of PYR all preparative processes were conducted in covered containers. In the HPLC system, a mobile phase of acetonitrile:water (30:70) with 0.6% (v/v) tri¯ouro acetic acid (TFA) pumped at ¯ow rate 1 mL/min was used for plasma samples and, acetonit- rile:water (15:85) with 0.6% (v/v) TFA pumped at ¯ow rate 1.4 mL/min was used for faecal samples. A Genesis nukleosil C 18 column (4 lm, 15 cm ´ 4.6 mm) (Jhones Chromatography, Mid Glamorgan, UK) was used with ultraviolet detection (model RF-10 A, Shimadzu, Kyoto, Japan) at a wavelength of 322 nm. Recovery of the drugs under study was measured by comparison of the peak areas from spiked plasma and faecal J. vet. Pharmacol. Therap. 24, 77±79, 2001. SHORT COMMUNICATION Ó 2001 Blackwell Science Ltd 77