Pharmacokinetic Evaluations of Sulpiride After Intravenous, Intramuscular, and Oral Single-Dose Administration in Jennies (Equus asinus)

Abstract

a b s t r a c tSulpiride is an antipsychotic human drug. It is commonly used to encourage ovulation in noncycling mares and to stimulate lactation in adoptive mares. No pharmacokinetic data are available for donkeys. The aim of this study was to assess the pharmacokinetics profile of sulpiride after intravenous (IV), intramuscular (IM), and oral (PO) administrations in healthy jennies. Animals (n ¼ 6) were treated with sulpiride, 1 mg/kg by IV, IM, and PO routes according to a randomized cross-over design (3 Â 3 Latin square). Blood samples (5 mL) were collected at predetermined times and analyzed using a validated high performance liquid chromatography with fluorescence detection method. IV and IM administrations gave similar curves, but they were not bioequivalent. The IM average bioavailability was 73.5%. After PO administration, the drug plasma concentrations were low and consequently both area under the curve and bioavailability (9.4%) were low. This finding could be because of the physicochemical 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 equine species whose gastric pH is particularly acidic. In conclusion, injective routes are definitely preferable to PO dosing because of the very low F% via this route.

Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

“…However, although interspecies allometric scaling needs further refinements and has limitations, it is still a potential tool and rational option for the estimate of pharmacokinetic parameters in species for which there are few data available (Huang & Riviere, ). The V ss of LSP in the current study was small, in agreement with those reported for sulpiride in the donkey and horse (Giorgi et al, , ). The V ss for LSP calculated in pharmacokinetic study in humans after IV administration (Xu et al, ) is higher than that in the present study but still moderate (1,300 ml/kg).…”

“…The lack of adverse effects in goats concurs with a previous studies in nurse mares and jennies (Giorgi et al, , ) and with the good tolerance previously reported in human subjects (Mauri, Bravin, Bitetto, Rudelli, & Invernizzi, ). This is also in‐line with clinical reports showing an excellent safety profile of sulpiride after 2 mg/kg once a day for a 3‐week treatment period (Panzani et al, ).…”

“…The current study found the clearance of LSP to be higher than those reported for sulpiride in horses and donkey (Giorgi et al, , ). However, the extraction ratio is low and it is similar to those calculated for equine species (Giorgi et al, , ), suggesting the same ability of these animal species to eliminate the drugs (Toutain & Bousquet‐Melou, ). Authors recognize that would have been better to experimentally evaluate Q ° value rather than calculate it by allometric scaling.…”

“…The procedure was based on a previously reported methods (Giorgi et al, , ). Briefly, in a 15 ml screw‐cap polypropylene vial, a 1 ml aliquot of plasma sample was added to 100 μl of IS (metoclopramide 0.25 μg/ml).…”

“…Sulpiride had been used in equine reproduction medicine: in treatment of fescue toxicosis (Redmond et al, 1994), to induce lactation in cycling and noncycling mares (Guillaume et al, ), and to hasten the first ovulation of the breeding season in noncycling mares (Duchamp & Daels, ). Further, pharmacokinetic studies of sulpiride have described its disposition in the horse, donkey, and rabbit (Fiorica et al, ; Giorgi, Ozdemir, Camillo, & Panzani, ; Giorgi et al, ). In equine, the sulpiride and LSP are clinically used as off‐label drugs in order to synchronize the ovulation phase.…”