Pharmacokinetics of intravenous, plain oral and enteric-coated oral omeprazole in the horse.

Abstract

The objectives were to document the pharmacokinetics of intravenous, enteric-coated oral and plain oral omeprazole in fasted horses and to investigate the impact of feeding on the bioavailability of an enteric-coated omeprazole. Twelve horses received four treatments: intravenous omeprazole (0.5mg/kg) in the fasted state (IV-Fasted), enteric-coated omeprazole (4mg/kg) orally in the fasted state (ECO-Fasted), enteric-coated omeprazole (4mg/kg) orally in the fed state (ECO-Fed) and plain omeprazole (4mg/kg) orally in the fasted state (PL-Fasted). Plasma omeprazole concentrations were determined by UHPLC-MS. Bioavailability was higher (P=0.038) in the ECO-Fasted group (21.5 [9.0-27.7]%) than the PL-Fasted group (10.1 [7.7-13.3]%). Similarly, AUC0-∞ was higher in the ECO-Fasted group than the PL-Fasted group (P=0.027). No significant differences were present between the ECO-Fasted and ECO-Fed groups with regards to bioavailability, Cmax , Tmax or AUC0-∞ . When the half-life data from the oral formulations was pooled, it was longer than that observed in the IV-Fasted group (100 [73-118] min) and 35 [34-39] min, respectively; P<0.0001). Bioavailability of enteric-coated omeprazole was higher than previously reported and feeding had minimal impact. Bioavailability of plain omeprazole was approximately half that of enteric-coated omeprazole. The longer half-life observed following oral administration was consistent with the flip-flop effect and has not previously been described for omeprazole in the horse.