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Sulpiride (SLP) is an antipsychotic drug used in humans. Although no pharmacokinetic data are available for horses, it is commonly used to encourage ovulation in noncycling mares and to stimulate lactation in adoptive mares. The aim of this study is to assess the pharmacokinetics profile of SLP after intravenous (IV), intramuscular (IM), and oral (PO) administrations in normal horses. Animals (n = 6) were treated with 1 mg/kg SLP, administered by IV, IM, and PO routes according to a randomized crossover design (3 × 3 Latin square). Blood samples (5 mL) were collected at a programmed time and analyzed using a validated with fluorescence detection method. SLP was present at a detectable concentration up to 24 hours postadministration for all routes, except for one animal in the PO group. IV and IM administrations gave similar curves, with an IM average bioavailability of 118.0%. These high values were mainly the result of the profile generated by two horses, in which a secondary concentration peak occurred in the terminal phase of the curve. After PO administration, AUC0-∞, and consequently bioavailability (20.4%), was low. This finding could be owing to the physicochemical features of the drug. Indeed, considering that SLP is a weak base, existing in the ionized form at gastric and physiological pH, it is unsurprising that it is poorly absorbable, especially in horses with a particularly acidic gastric pH. In conclusion, injective routes are definitely preferable to PO dosing because of the low bioavailability using this route.