Pharmacokinetic disposition and faecal excretion of pyrantel embonate following oral administration in horses.

Abstract

Pyrantel (PYR) is an imidazothiazole derivative, which belongsto the tetrahydropyrimidine class of anthelmintics. It is availableas tartrate and pamoate (syn. embonate) salts. Different salts ofPYR have different pharmacokinetic properties and consequentlydifferent toxicities to the host. The pamoate salt is almostinsoluble in water and poorly absorbed from the gastrointestinaltract and most passes unchanged in the faeces (Arundel, 1983).Reduced systemic absorption of the pamoate form potentiallyincreases availability in the lumen of the intestine (Bjorn et al.,1996). The tartrate salt of PYR is soluble in water and absorbedrapidly and extensively from the intestine of monogastricanimals (Faulkner et al., 1972).Pyrantel is highly effective (95–97%) against small strongyles,Parascaris equorum and Strongylus vulgaris, and has moderateactivity against Strongylus edentatus (70%) and Oxyuris equi(65%) (Mirck, 1985). Continuous (30 days) low-level dailyadministration of PYR tartrate (2.65 mg/kg) to horses washighly effective against common gastrointestinal parasitic infec-tions of horses, including large strongyles (S. vulgaris, S. edentatusand Triodontophorus spp.), adult small strongyles (Cyathostomumspp., Cylicocyclus spp., and Cylicostephanus spp.), and adult andfourth-stage P. equorum (Valdez et al., 1995).There is a paucity of data available in the literature on thepharmacokinetics of PYR in horses. In the present study, thepharmacokinetic disposition and faecal excretion of PYRembonate are reported in horses after oral administration.Eight thoroughbred gelding horses weighing 525–570 kgwere used in this study. Animals were kept at pasture during theexperimental period. Horses were identified by unique freezebrand or natural markings. A commercially available equineformulation of PYR embonate (Strongid-P, 43.9%, Pfizer Ltd,Kent, UK) was administered orally as a single bolus dose at13.3 mg/kg bodyweight to each animal. Heparinized bloodsamples were collected by jugular venipuncture prior to drugadministration and at 1, 2, 4, 8, 12, 20, 24, 32, 48, 72, 96 and120 h thereafter. Faecal samples (> 10 g) were also collectedper rectum (p.r.) throughout the blood sampling period, beforedrug administration and then 4, 8, 12, 20, 24, 32, 48, 72, 96and 120 h later in order to determine the faecal excretion. Thesamples were taken under Home Office Regulations (AnimalScientific Procedure Act, 1986). Blood samples were centrifugedat 1825 g for 30 min and the recovered plasma was transferredto plastic-stoppered tubes. All plasma and faeces samples werestored 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 extractionprocedure used for PYR was adapted from that described byMcKellar et al. (1993). Briefly, 1 mL drug-free plasma sampleswere fortified with PYR standard to reach the following finalconcentrations: 0.005, 0.01, 0.05, 0.1 and 0.5 lg/mL. Morantelcitrate was used as an internal standard. Sodium hydroxide(NaOH) (0.5 mL, 0.4