Pharmacokinetics of Sulpiride Following Intravenous, Intramuscular and Oral Single Dose Administration in Nurse Mares

Sulpiride is an antipsychotic human drug. Although no pharmacokinetic data is available for horses, it is commonly used to encourage ovulation in non-cycling mares and to stimulate lactation in adoptive mares. The aim of this study is to assess the pharmacokinetics profile of sulpiride after intravenous (IV) intramuscular (IM) and oral (PO) administrations in normal horses. Animals (n=6) were treated with sulpiride, 1 mg/kg by IV, IM and PO routes according to a randomized cross-over design (3x3 Latin-square). Blood samples (5 mL) were collected at programmed time and analyzed using a validated HPLC with fluorescence detection method. Sulpiride was present at a detectable concentration up to 24 h post-administration 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 where a secondary concentration peak occurred in the terminal phase of the curve. Following PO administration, AUC0- and consequently bioavailability (20.4%), was low. This finding could be due to the physico-chemical features of the drug. Indeed, considering that sulpiride 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 whose gastric pH is particularly acidic. In conclusion, injective routes are definitely preferable to oral dosing because of the very low F% via this route.