Pharmacokinetics of levosulpiride after single-dose administration by different routes in sheep (Ovis aries Linnaeus)

Levosulpiride (LSP) is the (−)-enantiomer of sulpiride and might represent a valid alternative to the current drugs used for the synchronization in small ruminants. The aim of this study was to provide the pharmacokinetic profile of LSP after intravenous (IV), intramuscular (IM) and oral (PO) administration in sheep. Six healthy female sheep underwent a randomized cross over study design with a wash out period of 1 week. Each animal at the completion of the study received 50 mg of LSP by IV, IM and PO administrations. Plasma samples were collected prior and up to 24 h and, after the extraction procedure, samples were analysed by HPLC with spectrofluorometric detection. LSP concentrations were quantifiable until 10 and 8 h after IV and IM administration, respectively. After PO administration plasma concentrations were low and quantified until 4 h in all the animals. Clearance (121.5 ml/Kg) was fast and volume of distribution (241 ml/Kg h) small; half-life was short and very similar after both IV (1.80 h) and IM (1.66 h) administrations. The bioavailability after IM and PO was high (about 70%) and extremely low (about 6%), respectively. IV and IM groups showed a good correlation between AUC and the LSP dose express in mg/Kg, but very low correlation was found for the PO route. In conclusion, PO administration of LSP is not recommended in sheep while IV and IM administration show comparable PK profiles.